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mysticalpeacenut · 3 months ago

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Advancements in PPI Targeted Drug Discovery

In the ever-evolving international of drug discovery, concentrated on protein-protein interactions (PPIs) has emerged as a groundbreaking method with massive healing capacity. While traditional drug discovery has largely focused on focused on single proteins or enzymes, the point of interest is shifting toward the intricate networks fashioned by using protein interactions. These networks are critical to expertise disorder mechanisms and growing innovative treatments. This blog delves into the modern day advancements in PPI targeted drug discovery, highlighting the transformative impact of Protein-Protein Interactions Magna™ technology and different modern tactics.

Understanding Protein-Protein Interactions

Protein-protein interactions are essential to almost each biological manner. Proteins not often function in isolation; as a substitute, they interact with different proteins to carry out their functions. These interactions can manipulate cell signaling pathways, adjust gene expression, and influence cell responses to environmental changes. Disruptions or malfunctions in those interactions are frequently implicated in diseases which include cancer, neurodegenerative problems, and infectious diseases.

PPI Targeted Drug Discovery makes a speciality of designing drugs which could especially modulate these protein interactions. Unlike conventional capsules that focus on a single protein, PPI-centered pills purpose to persuade the interactions among multiple proteins, thereby imparting a greater nuanced approach to therapeutic intervention.

Key Advancements in PPI Targeted Drug Discovery

Protein-Protein Interactions Magna™ Technology

One of the maximum giant advancements in PPI-focused drug discovery is the development of Protein-Protein Interactions Magna™ technology via Depixus. This modern day era gives a complete platform for analyzing and manipulating protein interactions with remarkable precision.

Magna™ generation uses advanced techniques to seize and examine how proteins engage within a cellular surroundings. By offering special insights into these interactions, Magna™ permits researchers to become aware of ability drug goals and design molecules that may in particular disrupt or decorate those interactions. This method is vital for growing healing procedures that focus on complicated sicknesses wherein conventional drug discovery methods may additionally fall brief.

High-Throughput Screening

High-throughput screening (HTS) has revolutionized PPI-centered drug discovery via permitting the rapid evaluation of lots of compounds for their capability to modulate protein interactions. HTS structures use automated structures to test big libraries of molecules against particular PPIs, identifying promising applicants for further development.

Recent improvements in HTS technology have expanded the speed and accuracy of screening processes. Innovations consisting of miniaturized assays, stepped forward detection techniques, and sophisticated statistics analysis gear have substantially better the efficiency of PPI-targeted drug discovery.

Structural Biology Techniques

Structural biology strategies, together with X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy, have supplied vital insights into the three-dimensional structures of protein complexes. Understanding the ideal structure of protein-protein interactions is essential for designing drugs which could in particular goal those interactions.

Recent traits in structural biology have enabled researchers to visualize protein interactions at atomic resolution, facilitating the design of small molecules and biologics which could efficiently disrupt or stabilize those interactions. This structural records is invaluable for growing centered treatment options with high specificity and decreased off-goal outcomes.

Computational Approaches

Computational methods, which includes molecular docking and molecular dynamics simulations, have end up necessary gear in PPI-targeted drug discovery. These techniques use pc algorithms to predict how small molecules or peptides will interact with protein complexes, guiding the layout of recent drugs.

Advancements in computational techniques have improved the accuracy of predictions and the efficiency of digital screening techniques. By simulating protein interactions and drug binding, researchers can pick out ability drug applicants and optimize their homes earlier than conducting experimental research.

Biologics and Peptide-Based Therapies

Biologics, along with monoclonal antibodies and peptide-based totally remedies, constitute a growing vicinity of hobby in PPI-focused drug discovery. These cures are designed to specially bind to protein interactions and modulate their activity.

Recent advancements in biologics and peptide design have caused the development of novel drugs that concentrate on PPIs with excessive specificity. For instance, bispecific antibodies which could simultaneously bind to two exclusive proteins are being explored as potential cures for numerous sicknesses.

The Future of PPI Targeted Drug Discovery

The subject of PPI focused drug discovery is swiftly advancing, with ongoing research aimed toward overcoming current challenges and increasing the range of druggable objectives. The integration of new technology, which includes Protein-Protein Interactions Magna™, structural biology, excessive-throughput screening, and computational strategies, is riding innovation and opening up new possibilities for therapeutic intervention.

As researchers hold to explore the complexities of protein interactions, the capability for growing novel treatments that concentrate on previously undruggable sicknesses grows. The capability to especially modulate protein-protein interactions offers a brand new stage of precision in drug development, paving the way for extra effective and focused remedies.

Conclusion

PPI focused drug discovery represents a paradigm shift in how we technique drug development, shifting beyond traditional single-protein objectives to focus on the tricky networks of protein interactions. With advancements which include Protein-Protein Interactions Magna™ era and other present day tactics, the sector is poised for great breakthroughs so one can remodel the landscape of medicine. At Depixus, we're at the leading edge of this thrilling field, providing innovative solutions and technologies that aid researchers of their quest to broaden the next generation of centered healing procedures. To study extra approximately how our Protein-Protein Interactions Magna™ generation can decorate your research and pressure innovation contact us at Depixus.

Reposted Blog Post URL: https://petrickzagblogger.wordpress.com/2024/09/04/advancements-in-ppi-targeted-drug-discovery/

#PPI Targeted Drug Discovery #Protein-Protein Interactions Magna™#PPI Technology #PPI Molecule #PPI Drug Discovery

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mtozbiolabs · 25 days ago

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Fusion Protein Interaction Analysis Service

Unlocking Hidden Functions: Advanced Fusion Protein Interaction Analysis Service

A Fusion Protein Interaction Analysis Service is a specialized offering that provides detailed insights into how fusion proteins (engineered proteins created by joining two or more genes originally coded for separate proteins) interact with other molecules or proteins.

Studying new proteins and their interactions can reveal potential functions that were previously unknown, opening up new directions in biological research.

One commonly used method for exploring PPIs is the pull-down assay, a reliable technique for identifying protein interactions in a sample.

Scientists can analyze functions more efficiently and accurately by isolating specific protein interactions.

The Pull-Down Assay: An Overview

The pull-down assay is a widely used technique in protein research, valued for its effectiveness in detecting specific PPIs.

The core concept involves using a “bait” protein, purified and enriched to interact selectively with a “target” protein in a sample.

This interaction allows researchers to capture proteins that bind to the bait, thus identifying potential interaction partners.

The pull-down assay significantly improves the efficiency of identifying new target proteins, eliminating non-specific interactions that could obscure results.

vimeo

Setting Up The Pull-Down Assay

The first step in a pull-down assay involves the preparation of the bait protein. This protein is typically modified with tags, such as poly-His or biotin tags, to facilitate binding to an immobilized affinity ligand.

These ligands are then attached to a solid-phase matrix, creating a stable surface for interaction. Once the bait protein is immobilized, it is mixed with a protein sample that potentially contains the target protein.

The bait protein specifically captures the target protein from this mixture through selective binding.

This interaction isolates the target protein from thousands of other proteins in the sample, allowing researchers to focus on the proteins of interest.

Isolation And Analysis Of Target Proteins

After the pull-down assay successfully captures the target protein, the next step is to identify it.

This is typically achieved through mass spectrometry, a technique that allows precise identification based on the protein’s mass and structure.

By using mass spectrometry, researchers can confirm the presence and identity of the target protein and gather information about its structure and function.

Combining pull-down assays and mass spectrometry thus provides a powerful approach for studying protein functions and interactions.

Advanced Tools And Services For Protein Analysis

With advancements in biotechnology, pull-down assays have become more efficient and accurate.

Companies like MtoZ Biolabs utilize specialized pull-down assay kits, such as those from Cell Signaling Technology (CST), in combination with advanced UPLC-MS platforms.

This setup enables fast and precise protein analysis, supporting researchers to understand PPIs more deeply. MtoZ Biolabs’ pull-down protein analysis service is a valuable tool for researchers looking to streamline their studies and achieve high-quality results in protein interaction analysis.

Conclusion

Protein-protein interactions are fundamental to understanding cellular function and biology.

The pull-down assay offers a practical approach to identifying specific PPIs, enabling scientists to investigate the roles of individual proteins and their contributions to more extensive biological processes.

Researchers can more accurately characterize protein interactions by combining the pull-down assay with advanced analytical tools and unveil new insights into protein functions.

These insights can lead to significant advancements in molecular biology, biochemistry, and medical research, contributing to our understanding of complex cellular mechanisms.

Have a peek at this website for getting more information related to Protein Interaction Analysis Services.

#Vimeo

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conchlifescience · 4 months ago

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Best Nutraceutical Manufacturing Company in India

Best Nutraceutical Manufacturing Company in India- India is diverse and one of the most developed countries with industry in almost every sector. The food industry is also growing. It has been stated that this nutraceutical market was valued at approximately USD 4.5 billion in 2017 and is expected to grow at a significant CAGR of 21% to reach USD 10.5 billion in 2022 and is expected to reach USD 18 billion by the end of 2025.

Conch Lifescience is a leading Nutraceutical Manufacturing Company in India. We have a credible name in the market for manufacturing quality nutraceutical products with AYUSH and FSSAI approvals. Our Nutraceutical Products are in high demand in the market. We follow a customer-centric approach to fulfil various requirements of nutraceutical products. these aspects make Conch Lifesciences one of the Best Nutraceutical manufacturers in India.

What Makes Conch Lifesciences The Best Nutraceutical Manufacturing Company in India?

At Conch Lifescience, we have built a strong position in the competitive Nutraceutical supplement and product market with our commitment to quality.

1. Patented & Imported Ingredients

Conch Lifescience is the Best Nutraceutical Manufacturing Company in India that uses proprietary ingredients to maintain the high quality of our products. We import raw materials mainly from the USA and Europe.

2. New Molecules

With a vigorous focus on research and innovation, Our professionals innovate new molecules with high efficiency and safety.

3. Latest & Innovative Packaging

At Conch Lifesciences, all products are available in an innovative packaging design that has also been tested for durability and shelf life.

4. Scientific Promotional Material

We provide the best scientific promotional material for the promotion and marketing of our nutraceutical products.

5. Wide Range Of Approvals

Conch Lifescince is duly approved by the authorities to manufacture and market Nutraceutical products.

6. Fast Delivery

We ensure timely delivery of all our nutraceutical products across PAN India to meet the client’s requirements.

Manufacturing Process

With our production services, we focus on providing our customers with production services at a reasonable price and a selection of the highest quality nutritional products. We are the most credible third-party Nutraceutical Manufacturing Company in India, but that doesn't mean we compromise on the quality of nutritional products. The steps involved in our manufacturing process are mentioned below:

Finalizing Composition And Order Quantity

Setting Products Quotation

Required Documents Submission

Finalizing Packing Material

Product Manufacturing

Product Delivery

Our Quality-Assured Product Range For Nutraceutical Manufacturing In India

Being a leading Nutraceutical Manufacturing Company in India, we produce high-quality Nutraceuticals. Furthermore, the products we manufacture are manufactured after extensive research by our highly experienced RandD team. That is why our products are considered the best products in the nutritional market and our products are also preferred by the masses. We have almost all types of nutritional product lines that come in different forms such as; granules, sachets, Soft gel, tablets, capsules, syrups, powder, etc. Here are the product categories we offer in India and other countries.

PPI & Antacids

Anti-Pyretic & Analgesic & Anti-Allergy

Anti-Cough & Anti-Cold

Syrups & Suspensions

Protein Powder & Energy Drink

Multi-Vitamins & Minerals

Antibiotics

Injectables

Herbal & Ayurvedic Products

Gels & Roll On & Creams

Why Choose Conch Lifescience For Nutraceutical Product Manufacturing?

Excellent quality, attractive packaging and timely delivery. We understand that everyone has their own unique business goals and ways to achieve market value. Conch Lifescience meets the requirements of every business. Conch Lifescience was founded by people who are passionate about the power of Nutraceutical Products. With decades of experience, innovation and dedicated dedication to creating a healthier lifestyle and getting stronger. Our company supports the desire to succeed in this field through our extensive research and development, focusing on innovation, collaboration with healthcare providers and advancing the science of Nutraceuticals. All these aspects of Third Party Manufacturing make Conch Lifesciences the best Nutraceutical Manufacturing Company in India.

#nutraceuticals #nutraceutical manufacturers

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gastroenterologyucgconferences · 7 months ago

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Getting to Digestive Health: A Comprehensive Guide to Gastroenterology Treatment

Introduction:

The field of gastroenterology encompasses a wide range of disorders affecting the digestive system, from common ailments like acid reflux and constipation to more serious conditions such as inflammatory bowel disease and liver disease. In this blog, we'll explore the diverse landscape of gastroenterology treatment, covering everything from lifestyle interventions to advanced medical therapies and surgical procedures aimed at promoting digestive health and well-being.

Lifestyle Modifications:

Many gastrointestinal disorders can be effectively managed through simple lifestyle modifications. Dietary changes, such as avoiding trigger foods, increasing fiber intake, and reducing alcohol consumption, can help alleviate symptoms of conditions like gastroesophageal reflux disease (GERD), irritable bowel syndrome (IBS), and inflammatory bowel disease (IBD). Additionally, maintaining a healthy weight, regular exercise, and stress management techniques can contribute to overall digestive health.

Medications:

Pharmacotherapy plays a crucial role in the treatment of various gastrointestinal conditions, providing relief from symptoms and reducing inflammation. Antacids, proton pump inhibitors (PPIs), and H2-receptor antagonists are commonly prescribed for acid-related disorders like GERD and peptic ulcers. Anti-inflammatory medications, immunosuppressants, and biologic agents are used to manage inflammatory conditions such as IBD and autoimmune hepatitis. Additionally, laxatives, antidiarrheal agents, and antibiotics may be prescribed for conditions like constipation, diarrhea, and bacterial overgrowth.

Endoscopic Interventions:

Endoscopy is a minimally invasive procedure used to visualize and treat abnormalities within the gastrointestinal tract. Endoscopic interventions can be therapeutic, allowing for the removal of polyps, treatment of bleeding ulcers, dilation of strictures, and placement of stents to relieve obstruction. Advanced endoscopic techniques, such as endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD), are employed for the treatment of early-stage gastrointestinal cancers and precancerous lesions.

Surgical Procedures:

In cases where conservative treatments fail to provide relief or complications arise, surgical intervention may be necessary. Gastrointestinal surgery encompasses a wide range of procedures, including laparoscopic and open surgeries for conditions such as appendicitis, gallstones, and colorectal cancer. Bariatric surgery is performed for the management of obesity and related comorbidities, while liver transplantation may be indicated for end-stage liver disease.

Emerging Therapies:

Advances in gastroenterology continue to drive the development of innovative therapies for challenging gastrointestinal conditions. Biologic therapies targeting specific molecules involved in inflammation have revolutionized the management of IBD, offering improved efficacy and safety compared to traditional immunosuppressants. Additionally, fecal microbiota transplantation (FMT) has emerged as a promising treatment for recurrent Clostridioides difficile infection and may hold potential for other gastrointestinal disorders.

Profession: Gastroenterologists are medical doctors who specialize in diagnosing and treating disorders of the digestive system. This includes conditions affecting the esophagus, stomach, small intestine, colon, rectum, pancreas, gallbladder, bile ducts, and liver.

Here are some key aspects of the profession of gastroenterology treatment:

Education and Training: Gastroenterologists undergo extensive education and training. After completing medical school, they typically undergo a residency in internal medicine followed by a fellowship in gastroenterology, which focuses on the diagnosis and treatment of digestive system disorders.

Diagnostic Procedures: Gastroenterologists use various diagnostic procedures to assess digestive system health, including endoscopy, colonoscopy, sigmoidoscopy, and imaging tests such as ultrasound, CT scans, and MRIs.

Treatment Modalities: Gastroenterologists employ a variety of treatment modalities to manage digestive system disorders. This may include medications, lifestyle modifications, dietary changes, endoscopic procedures, and, in some cases, surgery.

Specialized Areas: Within gastroenterology, there are subspecialties that focus on specific aspects of digestive health, such as hepatology (liver diseases), inflammatory bowel disease (Crohn's disease and ulcerative colitis), gastroesophageal reflux disease (GERD), and motility disorders.

Collaboration: Gastroenterologists often work closely with other healthcare professionals, including primary care physicians, surgeons, dietitians, and radiologists, to provide comprehensive care to patients with digestive system disorders.

Research and Innovation: Gastroenterologists are involved in research to advance the understanding and treatment of digestive system disorders. They may contribute to clinical trials, publish scientific papers, and participate in medical conferences to share knowledge and best practices.

Conclusion:

From lifestyle modifications and medications to endoscopic interventions and surgical procedures, gastroenterology treatment encompasses a diverse array of therapeutic modalities aimed at promoting digestive health and well-being. By embracing a comprehensive approach that addresses the underlying causes of gastrointestinal disorders and tailors treatment to individual patient needs, gastroenterologists can help patients navigate the path to optimal digestive health and quality of life.

Important Information:

Conference Name: 14th World Gastroenterology, IBD & Hepatology Conference Short Name: 14GHUCG2024 Dates: December 17-19, 2024 Venue: Dubai, UAE Email: [email protected] Visit: https://gastroenterology.universeconferences.com/ Call for Papers: https://gastroenterology.universeconferences.com/submit-abstract/ Register here: https://gastroenterology.universeconferences.com/registration/ Exhibitor/Sponsor: https://gastroenterology.universeconferences.com/exhibit-sponsor-opportunities/ Call Us: +12073070027 WhatsApp Us: +442033222718

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whats-in-a-sentence · 2 years ago

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Glutamine synthetase (GS) combines ammonium with glutamate to form glutamine (Figure 13.7A):

Glutamate + NH4+ + ATP → glutamine + ADP + Pi

This enzyme transfers the amide group of glutamine to 2-oxoglutarate, yielding two molecules of glutamate (see Figure 13.7A). (...) Glutamate dehydrogenase (GHD) catalyzes a reversible reaction that synthesizes or deaminates glutamate (Figure 13.7B):

2-oxoglutarate + NH4+ + NAD(P)H <—> glutamate + H2O + NAD(P)+

(...) Although both forms are relatively abundant, they cannot substitute for the GS-GOGAT pathway for assimilation of ammonium, and their primary function is in deaminating glutamate during the reallocation of nitrogen (see Figure 13.7B). (...) An example of aspartate aminotransferase (Asp-AT), which catalyzes the following reaction (Figure 13.7C):

Glutamate + oxaloacetate → 2-oxoglutarate + aspartate

in which the amino group of glutamate is transferred to the carboxyl group of oxaloacetate. (...) The major pathway for asparagine synthesis involves the transfer of the amide nitrogen from glutamine to aspartate (Figure 13.7D):

Glutamine + aspartate + ATP → glutamate + asparagine + AMP + PPi

"Plant Physiology and Development" int'l 6e - Taiz, L., Zeiger, E., Møller, I.M., Murphy, A.

#book quotes #plant physiology and development #nonfiction #textbook #glutamate #aspartate #asparagine #synthesis #ammonium

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greatreviewreview · 3 years ago

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What to know about peptides for health

Peptides are smaller versions of proteins. Many health and cosmetic products contain different peptides for many uses, such as their potential anti-aging, anti-inflammatory, or muscle building properties.

Recent research indicates that some types of peptides could have a beneficial role in slowing down the aging process, reducing inflammation, and destroying microbes.

People may confuse peptides with proteins. Both proteins and peptides are made up of amino acids, but steroids powder contain far fewer amino acids than proteins. Like proteins, peptides are naturally present in foods.

Due to the potential health benefits of peptides, many supplements are available that contain peptides that manufacturers have derived either from food or made synthetically.

Some of the most popular peptides include collagen peptides for anti-aging and skin health, and creatine peptide supplements for building muscle and enhancing athletic performance.

In this article, we discuss the potential benefits and side effects of peptide supplements.

Peptides are short strings of amino acids, typically comprising 2–50 amino acids. Amino acids are also the building blocks of proteins, but proteins contain more.

Peptides may be easier for the body to absorb than proteins because they are smaller and more broken down than proteins. They can more easily penetrate the skin and intestines, which helps them to enter the bloodstream more quickly.

Scientists are most interested in mechano growth factor peptide, or those that have a beneficial effect on the body and may positively impact human health.

Different bioactive peptides have different properties. The effects they have on the body depend on the sequence of amino acidsTrusted Source they contain.

Some of the most common peptide supplements available are:

Collagen peptides, which may benefit skin health and reverse the effects of aging.

Creatine peptides, which may build strength and muscle mass.

Some people may take other peptides and peptide hormones to enhance athletic activity. However, the World Anti-Doping Agency have banned many of these, including follistatin, a peptide that increases muscle growth.

Collagen is a protein in the skin, hair, and nails. Collagen peptides are broken down collagen proteins that the body can absorb more easily. Taking collagen peptides may improve skin health and slow the aging process.

Some studiesTrusted Source indicate that dietary food supplements that contain collagen peptides can treat skin wrinkles. Other research indicates that these supplements may also improve skin elasticity and hydration.

Peptides may stimulate the production of melanin, a skin pigment, which may improve the skin’s protection against sun damage.

Topical anti-aging cosmetics can also contain Melanotan Peptide, which manufacturers claim can reduce wrinkles, help skin firming, and increase blood flow.

Improve wound healing

As collagen is a vital component of healthy skin, collagen peptides may facilitate faster wound healing.

Bioactive peptides can also reduce inflammation and act as antioxidants, which can improve the body’s ability to heal.

Research is currently ongoing into antimicrobial peptides, which may also improve wound healing. Having very high or very low levels of some antimicrobial peptides may contribute to skin disorders, such as psoriasis, rosacea, and eczema.

Prevent age-related bone loss

Animal research links a moderate intake of collagen peptides with an increase in bone mass in growing rats who also did running exercise.

The study may point to collagen peptides being a useful way to counteract age-related bone loss. However, more research is necessary, especially on humans.

Build strength and muscle mass

Some researchTrusted Source on older adults indicates that collagen peptide supplements can increase muscle mass and strength. In the study, participants combined supplement use with resistance training.

Creatine peptides may also improve strength and help to build muscle.

While fitness enthusiasts have been using creatine protein powders for many years, creatine PEG MGF peptide are increasing in popularity.

These particular peptides may be easier for the body to digest, which means they may cause fewer digestive problems than creatine proteins.

For healthy individuals, peptide supplements are unlikely to cause serious side effects because they are similar to the peptides present in everyday foods.

Oral peptide supplements may not enter the bloodstream as the body may break them down into individual amino acids.

In one studyTrusted Source where females took oral collagen peptide supplements for 8 weeks, the researchers did not note any adverse reactions.

However, the United States Food and Drug Administration (FDA) do not regulate supplements in the same way they do medications. As a result, people should exercise caution when taking any supplements.

Topical creams and ointments containing peptides may cause skin symptoms, such as skin sensitivity, rash, and itching.

Individuals should always buy from a reputable company and discontinue use if adverse reactions occur.

Also, it is a good idea to speak to a doctor before taking peptide supplements or using topical products that contain peptides.

Those who are pregnant, breastfeeding, taking medications, or living with a medical condition should avoid using peptides until they speak to their doctor.

The timing and dose of peptide supplements will vary, depending on the type and brand.

Always follow the package instructions when taking peptide supplements or using topical peptide creams or lotions. Never exceed the recommended serving size. Discontinue use and consult a doctor if adverse reactions occur.

Peptides are naturally present in protein-rich foods. It is not necessary to take peptide supplements or use topical sources of peptides.

However, some people may wish to use collagen peptides with the aim of slowing down the aging process. Others may take creatine peptides to build muscle and strength.

There is still limited evidence to indicate that these products are effective, and much more research is necessary to assess their efficacy and safety thoroughly.

Research into peptides is in the early stages, and in the future, scientists may discover health benefits of different types of peptides. Until then, people should exercise caution when taking any supplement and discuss the potential benefits and risks with their doctor beforehand.

Protein–protein interactions (PPIs) execute many fundamental cellular functions and have served as prime drug targets over the last two decades. Interfering intracellular PPIs with small molecules has been extremely difficult for larger or flat binding sites, as antibodies cannot cross the cell membrane to reach such target sites. In recent years, peptides smaller size and balance of conformational rigidity and flexibility have made them promising candidates for targeting challenging binding interfaces with satisfactory binding affinity and specificity. Deciphering and characterizing peptide–protein recognition mechanisms is thus central for the invention of peptide-based strategies to interfere with endogenous protein interactions, or improvement of the binding affinity and specificity of existing approaches. Importantly, a variety of computation-aided rational designs for peptide therapeutics have been developed, which aim to deliver comprehensive docking for peptide–protein interaction interfaces. Over 60 peptides have been approved and administrated globally in clinics. Despite this, advances in various docking models are only on the merge of making their contribution to peptide drug development. In this review, we provide (i) a holistic overview of peptide drug development and the fundamental technologies utilized to date, and (ii) an updated review on key developments of computational modeling of peptide–protein interactions (PepPIs) with an aim to assist experimental biologists exploit suitable docking methods to advance peptide interfering strategies against PPIs.

Delivering drugs specifically to patient neoplasms is a major and ongoing clinical challenge. Function-blocking monoclonal antibodies were first proposed as cancer therapies nearly four decades ago. The large size of these molecules hindered their commercial development so that the first antibody or antibody-fragment therapies were only commercialized for cancer therapeutics and diagnostics 20 years later [1,2]. A classic development during this period, a radiolabelled peptide analog of somatostatin (SST) was used to target neuroendocrine tumors expressing the SST receptor instead of targeting the receptor with an antibody [3]. The concept of using a peptide as a targeting moiety for cancer diagnosis and treatment has since led to current peptide drug developments in both academia and pharmaceutical industries. In addition to cancer treatments, melanotan 2 peptide that mimic natural peptide hormones also offer therapeutic opportunities. Synthetic human insulin, for instance, has been long exemplified for its clinical efficacy for diabetic patients [4].

In comparison to small molecules, such as proteins and antibodies, peptides indeed represent a unique class of pharmaceutical compounds attributed to their distinct biochemical and therapeutic characteristics. In addition to peptide-based natural hormone analogs, peptides have been developed as drug candidates to disrupt protein–protein interactions (PPIs) and target or inhibit intracellular molecules such as receptor tyrosine kinases [5,6]. These strategies have turned peptide therapeutics into a leading industry with nearly 20 new peptide-based clinical trials annually. In fact, there are currently more than 400 peptide drugs that are under global clinical developments with over 60 already approved for clinical use in the United States, Europe and Japan.

Protein–protein interactions (PPIs) are the foundation of essentially all cellular process. Those biochemical processes are often comprised of activated receptors that indirectly or directly regulate a series of enzymatic activities from ion transportation, transcription of nucleic acids and various post-translational modifications of translated proteins [7]. Drugs that bind specifically to such receptors can act as agonists or antagonists, with downstream consequences on cellular behavior. Peptides and small molecules that interfere with PPIs are thus in high demand as therapeutic agents in pharmaceutical industries due to their potential to modulate disease-associated protein interactions. Accumulating evidence has suggested that better identification of targetable disease-associated PPIs and optimization of peptide drug binding characteristics will be key factors for their clinical success [8].

Unfortunately, understanding the molecular recognition mechanism and delineating binding affinity for PPIs is a complex challenge for both computational biologists and protein biochemists. This is largely because small molecules are superior in binding to deep folding pockets of proteins instead of the larger, flat and hydrophobic binding interfaces that are commonly present at PPI complex interfaces [9]. Although monoclonal antibodies are more effective at recognizing those PPI interfaces, they cannot penetrate the cell membrane to reach and recognize intracellular targets. In recent years, peptides with balanced conformational flexibility and binding affinity that are up to five times larger than small molecule drugs have attracted enormous attention [10,11]. Cyclic peptides, for example have small molecule drug properties like long in vivo stability, while maintaining robust antibody-like binding affinity and minimal toxicity [12]. In this review, we will focus two aspects of peptide drug development: (i) Fundamental technologies utilized for peptide drug developments to date, and (ii) key developments of computational modeling techniques in peptide–protein interactions (PepPIs). Recent topics and basics in conventional docking of PPIs will also be covered with an aim to assist experimental biologists exploiting suitable docking methods to advance peptide interfering strategies against PPIs.

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davidwalker2504 · 3 years ago

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The global Gastroesophageal Reflux Disease (GERD) therapeutics market size was valued at USD 5.66 billion in 2016 and by is estimated to be USD 4.34 billion by 2025, it is anticipated to observe a decrease in its revenue at a negative CAGR of -2.9%. Expiration of patented blockbuster drugs, which are indicated for the management of disorders of acid reflux is major restraining factors for this market.

With strong clinical pipelines and patent litigations, the market continues to experience significant changes. Proton pump inhibitors (PPI) and antagonists of histamine H2 receptor have the importance in current scenario of the market.

Upon loss of patent protection of formerly leading branded drugs, generic molecules with low-price can ingest the sales of the branded ones up to 90%. Rising number of companies being exposed to price scrutiny associated with shift in the focus of government on the promotion of consumer convenience will stimulate further reduction of drug prices. Although market turnover is affected by the expiration of major patents and the demand of drugs used to reduce acid, due to the increasing prevalence of heartburn, is anticipated to increase in the upcoming years.

#gastroesophageal reflux disease

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mysticalpeacenut · 1 month ago

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Comparing RNA vs. PPI Drug Discovery Methods

In the world of modern drug discovery, two cutting-edge approaches stand out: RNA-targeted drug discovery and PPI-targeted drug discovery. Both methods have the potential to revolutionize therapeutic development, offering novel ways to tackle diseases that were previously thought to be untreatable. Understanding the distinctions between these approaches, along with how MAGNA™ Technology plays a role in advancing them, sheds light on their respective strengths and applications in drug development.

Understanding RNA-Targeted Drug Discovery

RNA-targeted drug discovery is an innovative approach that focuses on interfering with RNA molecules to modulate gene expression and subsequently address disease mechanisms. RNA plays a crucial role in the transcription and translation processes, converting genetic information from DNA into proteins. By targeting RNA, scientists can intervene in this process before harmful proteins are produced, effectively tackling diseases at a more fundamental level.

This approach has gained considerable attention in recent years, particularly in the context of diseases like cancer, viral infections, and genetic disorders. RNA-targeted therapies offer the ability to modulate gene activity, suppress disease-causing genes, and enhance the body's ability to repair itself at a molecular level.

Key benefits of RNA-targeted drug discovery include:

The ability to influence diseases at their genetic roots.

The potential to treat a broad spectrum of conditions, including those involving previously "undruggable" targets.

Flexibility in targeting various RNA types, such as mRNA, siRNA, and lncRNA.

The development of drugs that target RNA has already seen successes in treatments for genetic diseases like spinal muscular atrophy (SMA) and amyotrophic lateral sclerosis (ALS). This method holds promise in expanding the range of treatable conditions, especially as our understanding of RNA biology grows.

Exploring PPI-Targeted Drug Discovery

On the other hand, PPI-targeted drug discovery focuses on disrupting protein-protein interactions (PPIs). Proteins frequently interact with one another to carry out biological processes, and these interactions are critical for the function of healthy cells. However, in the case of many diseases-particularly cancer and neurodegenerative disorders-these interactions become abnormal, leading to harmful cellular activities.

The objective of PPI-targeted drug discovery is to develop small molecules or biologics that can selectively disrupt or modulate these protein interactions. By doing so, it is possible to halt the disease-causing processes at their source.

PPIs were once considered difficult to target, mainly due to the large and often featureless interaction surfaces of proteins. However, advances in biomolecular insights and drug development technologies, such as MAGNA™ Technology, have made it more feasible to target these previously elusive interactions.

Benefits of PPI-targeted drug discovery include:

The ability to target diseases involving protein misfolding, aggregation, or abnormal protein networks.

Access to therapeutic targets that were once deemed undruggable.

Potential applications in treating complex diseases such as cancer, Alzheimer's, and autoimmune disorders.

RNA vs. PPI Drug Discovery: A Comparative Perspective

While both RNA-targeted and PPI-targeted drug discovery methods have the potential to transform modern medicine, they approach disease treatment from different angles. Here’s a comparison of the two:

1. Mechanism of Action:

RNA-targeted drug discovery aims to modulate gene expression by targeting RNA molecules before they are translated into proteins. This method can effectively prevent the synthesis of harmful proteins.

PPI-targeted drug discovery, on the other hand, focuses on disrupting harmful interactions between proteins, stopping disease-causing proteins from working together.

2. Disease Targets:

RNA-based therapies have shown great promise in treating genetic diseases, rare disorders, and viral infections, as well as certain cancers.

PPI-targeted therapies are particularly relevant in diseases where protein interactions go awry, such as cancers, neurodegenerative diseases, and immune system disorders.

3. Technological Innovations:

RNA-targeted therapies have benefited greatly from advancements in RNA delivery systems, such as lipid nanoparticles, which have improved the efficacy and safety of RNA-based drugs.

For PPI-targeted therapies, advancements in structural biology and MAGNA™ Technology have been instrumental in identifying and targeting key protein interactions that were previously considered undruggable.

4. Challenges:

RNA-targeted drug discovery faces challenges related to RNA instability and ensuring targeted delivery to specific tissues.

PPI-targeted therapies are still overcoming the complexities of identifying suitable binding sites on protein surfaces and ensuring specificity.

Both methods hold incredible potential, but the choice between them depends on the specific disease, target, and therapeutic goals. Researchers and pharmaceutical companies often explore both avenues to determine which approach offers the most effective solution for a particular condition.

MAGNA™ Technology: A Common Ground

MAGNA™ Technology, a platform developed by Depixus, plays a crucial role in both RNA and PPI drug discovery. This advanced technology allows researchers to study biomolecular interactions at an unprecedented level of detail, providing critical insights into how molecules such as RNA and proteins interact within cells. MAGNA™ enhances the ability to identify key targets and develop drugs that can modulate these interactions effectively.

In RNA-targeted drug discovery, MAGNA™ Technology helps scientists understand how RNA molecules interact with other cellular components, enabling the design of more precise and potent therapies. For PPI-targeted drug discovery, MAGNA™ provides valuable data on the structural and functional aspects of protein interactions, helping researchers develop drugs that can disrupt these interactions more effectively.

By facilitating deeper insights into molecular interactions, MAGNA™ Technology is driving innovation in both RNA and PPI drug discovery, bringing us closer to developing treatments for diseases that have long been resistant to traditional therapies.

Conclusion

In the dynamic field of drug discovery, both RNA-targeted and PPI-targeted drug discovery represent powerful approaches to addressing some of the most challenging diseases. With advancements in MAGNA™ Technology and our growing understanding of biomolecular interactions, the future of both methods looks incredibly promising. Whether by targeting RNA or disrupting protein interactions, these technologies hold the potential to revolutionize treatment options for patients worldwide.

For more information on how Depixus is leading the way in RNA and PPI drug discovery, feel free to contact us today!

Reposted Blog Post URL: https://zagpetrick.livepositively.com/comparing-rna-vs-ppi-drug-discovery-methods/

#RNA-targeted Drug Discovery #PPI-targeted Drug Discovery #Biomolecular Insights #MAGNA™ Technology #RNA and PPI Drug Discovery

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cool-akashy-maximize · 4 years ago

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Global Enzyme Inhibitors Market : Industry Analysis and Forecast (2019-2026)

Global Enzyme Inhibitors Market is expected to reach XX Billion by 2026 from 169.68 Billion in 2019 at CAGR of XX %.

The report includes the analysis of impact of COVID-19 lock-down on the revenue of market leaders, followers, and disrupters. Since lock down was implemented differently in different regions and countries, impact of same is also different by regions and segments. The report has covered the current short term and long term impact on the market, same will help decision makers to prepare the outline for short term and long term strategies for companies by region.

Global Enzyme Inhibitors Market

To know about the Research Methodology:-Request Free Sample Report

A molecule that binds to an enzyme and decreases its activity are the main function of enzyme inhibitors. Since blocking an enzyme's activity can kill a pathogen or correct a metabolic imbalance, many drugs are enzyme inhibitors, which is important considering market size. They are also used in pesticides giving an upper hand in field of medicine. Not all molecules that bind to enzymes are inhibitors; enzyme activators bind to enzymes and increase their enzymatic activity, while enzyme substrates bind and are converted to products in the normal catalytic cycle of the enzyme.

Enzyme Inhibitors drugs help to cure chronic diseases like cardiovascular disease, gastrointestinal disease, acquired immunodeficiency syndrome, cancer, hepatitis, men's-health-related conditions (erectile dysfunction, benign prostatic hyperplasia, alopecia), diabetes and various others (rheumatoid arthritis, psoriasis, Parkinson's disease, influenza, etc.) Enzyme Inhibitors have a huge application as drugs in therapeutics and pesticides for agricultural activities.

The market has witnessed significant growth based on outsourcing manufacturing process together with effective & accurate therapies for chronic diseases such as cancer, respiratory diseases, and others.

The Total market opportunity for Global Enzyme Inhibitors Market is divided into five key market segments that include:

• By Type • By Application • By Disease Indication • by End-Use Industry • By Geography The report has addresses and analyzed the market by five key geographies i.e.

• North America • Europe • Asia-Pacific • Middle East & Africa • Latin America APAC region is going to emerge as one of the faster-growing Global Enzyme Inhibitors Market in forecast period followed by North America and Europe. Global Enzyme Inhibitors Market Key Highlights:

• Assessment of market definition along with the identification of key players and analysis of their strategies to determine the competitive outlook of the market, opportunities, drivers, restraints, and challenges for Global Enzyme Inhibitors Market during the forecast period • Complete quantitative analysis of the industry from 2018 to 2026 to enable the stakeholders to capitalize on the prevailing market opportunities • In-depth analysis of the industry on the basis of market segments, market dynamics, market size, competition & companies involved value chain. • Global Enzyme Inhibitors Market analysis with respect to Type, Application, Disease Indication, On End-Use Industry and Geography to assist in strategic business planning. • Global Enzyme Inhibitors Market analysis and forecast for five major geographies North America, Europe, Asia Pacific, Middle East & Africa, Latin America and their key regions Years that have been considered for the study are as follows:

• Base Year - 2018 • Estimated Year - 2019 • Forecast Period - 2019 to 2026

For company profiles, 2018 has been considered as the base year. In cases, wherein information was unavailable for the base year, the years prior to it have been considered. Global Enzyme Inhibitors Market Research Methodology:

The objective of the report is to present comprehensive assessment projections with a suitable set of assumptions and methodology. The report helps in understanding Global Enzyme Inhibitors Market dynamics, structure by identifying and analyzing the market segments and projecting the global market size. Further, the report also focuses on the competitive analysis of key players by product, price, financial position, growth strategies, and regional presence. To understand the market dynamics and by region, the report has covered the PEST analysis by region and key economies across the globe, which are supposed to have an impact on market in forecast period. PORTER’s analysis, and SVOR analysis of the market as well as detailed SWOT analysis of key players has been done to analyze their strategies. The report will to address all questions of shareholders to prioritize the efforts and investment in the near future to the emerging segment in the Global Enzyme Inhibitors Market. Key Players in the Global Enzyme Inhibitors Market are:

• Astrazeneca Plc. • Boehringer Ingelheim International Gmbh • Cipla USA Inc • Daiichi-Sankyo Co. Ltd • Eisai Inc. • F.Hoffman-La Roche Ag • GlaxoSmithKline Plc • Incyte Corp • Koea Pharmaceuticals • Merck & Co.Inc • Novartis Holding Ag • Sanofi Genzyme Corp • Sun Pharmaceutical Industries Ltd. • Teva Pharmaceuticals Co. • VIII Healthcare • Zydus Cadila • Abbott Laboratories • Bayer Ag Global Enzyme Inhibitors Market Key Target Audience:

• Hospitals, diagnostic centers, homecare service providers, and medical colleges • Teaching hospitals and academic medical centers • Government bodies or municipal corporations • Suppliers and distributors of Enzyme Inhibitors

for more info:https://www.maximizemarketresearch.com/market-report/global-enzyme-inhibitors-market/3206/

The scope of the Global Enzyme Inhibitors Market : Inquire before buying

The research report segments North America Enzyme Inhibitors market based on Type, Application, Disease Indication, On End-Use Industry and Geography Global Enzyme Inhibitors Market (By Type):

• Proton Pump Inhibitors (PPIs) • Reverse Transcriptase Inhibitors • Kinase Inhibitors • Statins • Protease Inhibitors • Aromatase Inhibitors • Neuraminidase Inhibitors • Others. Global Enzyme Inhibitors Market (By Application):

• Chemotherapy • Antibiotics • Cardiovascular Treatments • Pesticides • Others. Global Enzyme Inhibitors Market (By Disease Indication):

• Chronic Obstructive Pulmonary Disorders • Gastrointestinal Disorders • Inflammatory Diseases • Cardiovascular Diseases • Arthritis • Others Global Enzyme Inhibitors Market (On End-Use Industry):

• Pharmaceutical • Biotechnology • Food & Beverages • Others Global Enzyme Inhibitors Market (By Geography):

• North America • Europe • Asia-Pacific • Middle East & Africa • Latin America Available Customization:

Maximize Market Research offers customization of report and scope of the report as per the specific requirement of our client.

For More Information Visit @: This Report Is Submitted By : Maximize Market Research Company Customization of the report: Maximize Market Research provides free personalized of reports as per your demand. This report can be personalized to meet your requirements. Get in touch with us and our sales team will guarantee provide you to get a report that suits your necessities.

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millioninsights · 4 years ago

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Gastroesophageal Reflux Disease (GERD) therapeutics market is estimated to be USD 4.34 billion by 2025

Industry Insights

The devices of GERD serves as a substitute for management of heartburn, because of low rate of success and failure in clinical trials. Hence, very limited acceptance of devices of GERD management contribute for the rising demand of drugs having acid neutralizing property, as the major therapy approach.

Nevertheless, the advent of devices which are minimally invasive to address anatomical defects are gaining popularity coupled with supportive evidence from clinical data for performing various procedures including trans oral fundoplication, which helps in preventing reflux of non-acid and acid contents. The adoption of these devices have been further reinforced in the U.S. in 2016 with the advent of a CPT code (43210) which helps in facilitating reimbursement process.

Drug Type Insights

In 2016, the second largest segment was found to be PPIs as it is the most common medication prescription type for the diseases such as heartburn. Generics inflow leading to the loss of exclusiveness of popular drugs, including Prilosec and Nexium, is estimated to negatively affect the sales of branded versions. A further decrease is appearing more with the expected expiration of other patented drugs, such as Dexilant.

Regional Insights

Moreover, outpatient clinic visits for GERD disorder in the U.S. has been increased in the past few years because of the more prone geriatric population to develop acid reflux and heartburn. On the contrary, the Asia Pacific is estimated to witness the fastest growth rate. The increasing geriatric population and dietary and lifestyle risk factors such as diet with high fat and obesity, is anticipated to drive the growth. In developing countries, the inclination towards self-medication is quickly increasing because of the affordability and availability of OTC antacids as in China and India.

Competitive Insights

Among others, RaQualia Pharma, Inc. and Ironwood Pharmaceuticals, Inc. are focusing more on development of new generic molecules, which involves novel and existing drug mechanisms as a part of the strategy to enter into the competition. Many generic players are also trying to focus on these spaces in an attempt to capture a larger share by the new version to replace the patent expired drugs.

Read full research report:

https://www.millioninsights.com/industry-reports/gastroesophageal-reflux-disease-gerd-therapeutics-market

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#Gastroesophageal Reflux Disease (GERD) Therapeutics #GERD #Healthcare #Antacids #H2 Receptor Blockers #Proton Pump Inhibitors

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newinnovationalmarketresearch · 4 years ago

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Gastroesophageal Reflux Disease (GERD) Therapeutics Market Share, Top Key Players, Price, Revenue and Growth Rate Forecast 2025

Request a Sample PDF Copy of This Report @ https://www.millioninsights.com/industry-reports/gastroesophageal-reflux-disease-gerd-therapeutics-market/request-sample

Market Synopsis of Gastroesophageal Reflux Disease (GERD) Therapeutics Market:

Drug Type Insights

View Full Table of Contents of This Report @ https://www.millioninsights.com/industry-reports/gastroesophageal-reflux-disease-gerd-therapeutics-market

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researchreportinsight · 4 years ago

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Gastroesophageal Reflux Disease Therapeutics Market 2025: Report Focusing on Opportunities, Revenue & Market Driving Factors

4th January 2021 – The global Gastroesophageal Reflux Disease (GERD)therapeutics market size was valued at USD 5.66 billion in 2016 and by is estimated to be USD 4.34 billion by 2025, it is anticipated to observe a decrease in its revenue at a negative CAGR of -2.9%. Expiration of patented blockbuster drugs, which are indicated for the management of disorders of acid reflux is major restraining factors for this market. With strong clinical pipelines and patent litigations, the market continues to experience significant changes. Proton pump inhibitors (PPI) and antagonists of histamine H2 receptor have the importance in current scenario of the market.

The devices of GERD serve as a substitute for management of heartburn, because of low rate of success and failure in clinical trials. Hence, very limited acceptance of devices of GERD management contributes for the rising demand of drugs having acid neutralizing property, as the major therapy approach. Nevertheless, the advent of devices which are minimally invasive to address anatomical defects are gaining popularity coupled with supportive evidence from clinical data for performing various procedures including trans oral fundoplication, which helps in preventing reflux of non-acid and acid contents. The adoption of these devices has been further reinforced in the U.S. in 2016 with the advent of a CPT code (43210) which helps in facilitating reimbursement process.

Access Gastroesophageal Reflux Disease (GERD) Therapeutics Market Report with TOC @ https://www.millioninsights.com/industry-reports/gastroesophageal-reflux-disease-gerd-therapeutics-market

In 2016, market was dominated by the antacids segment and is anticipated to keep its top position over the forecast period. Most preferred first-line therapy for infrequent and mild symptoms is antacids, as the therapy neutralizes the secretion of gastric acid immediately. Convenient OTC (over-the-counter) accessibility various forms such as syrups, powders and tablets is accountable for the extreme adoption. Moreover, the AHFS (American Hospital Formulary services), amongst other countries, enlisted over 120 preparations too advocate. In 2016, the second largest segment was found to be PPIs as it is the most common medication prescription type for the diseases such as heartburn. Generics inflow leading to the loss of exclusiveness of popular drugs, including Prilosec and Nexium, is estimated to negatively affect the sales of branded versions. A further decrease is appearing more with the expected expiration of other patented drugs, such as Dexilant.

In 2016, the largest region was found to be North America in terms of share for GERD market. Every year, GERD symptoms are experienced by more than 80 million people in the U.S., of which, approximately 25 million patients suffer from acid reflux and heartburn daily and approximately 60 million patients monthly. Moreover, outpatient clinic visits for GERD disorder in the U.S. has been increased in the past few years because of the more prone geriatric population to develop acid reflux and heartburn. On the contrary, the Asia Pacific is estimated to witness the fastest growth rate. The increasing geriatric population and dietary and lifestyle risk factors such as diet with high fat and obesity, is anticipated to drive the growth. In developing countries, the inclination towards self-medication is quickly increasing because of the affordability and availability of OTC antacids as in China and India.

Competitive market, which is generics-driven is creating a pressure on the prices of drug with decreased retail sales, which will stimulate stationary growth in future. Companies producing them range from high to medium on the basis of competitive rivalry. Eisai Co., Ltd.; AstraZeneca PLC; GlaxoSmithKline PLC; Johnson & Johnson and Takeda Pharmaceutical Co., Ltd.; are some of the top key players. In addition, Daewoong Pharmaceutical Co., Ltd.; SRS Pharmaceuticals Pvt. Ltd.; SFJ Pharmaceuticals Group and Ironwood Pharmaceuticals, Inc. are some emerging companies. Among others, RaQualia Pharma, Inc. and Ironwood Pharmaceuticals, Inc. are focusing more on development of new generic molecules, which involves novel and existing drug mechanisms as a part of the strategy to enter into the competition. Many generic players are also trying to focus on these spaces in an attempt to capture a larger share by the new version to replace the patent expired drugs.

Request a Sample Copy of Gastroesophageal Reflux Disease (GERD) Therapeutics Market Report @ https://www.millioninsights.com/industry-reports/gastroesophageal-reflux-disease-gerd-therapeutics-market/request-sample

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chitrakullkarni · 4 years ago

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Gastroesophageal Reflux Disease (GERD) Therapeutics Market Revenue Driving Factors, Global Trends and Forecast Report, 2025

The global Gastroesophageal Reflux Disease (GERD) Therapeutics Market research report provides complete insights on industry scope, global trends, regional estimates, key application, competitive landscape and financial performance of prominent players. It also offers ready, data-driven answers to several industry-level questions. This study enables numerous opportunities for the market players to invest in research and development.

Market Overview:

The global Gastroesophageal Reflux Disease (GERD) therapeutics market size was valued at USD 5.66 billion in 2016 and is estimated to be USD 4.34 billion by 2025, it is anticipated to observe a decrease in its revenue at a negative CAGR of -2.9%. Expiration of patented blockbuster drugs, which are indicated for the management of disorders of acid reflux is major restraining factors for this market.

Key Players:

Takeda Pharmaceutical Co., Ltd.

AstraZeneca PLC

Eisai Co., Ltd.

GlaxoSmithKline PLC.

Johnson & Johnson Services, Inc.

Daewoong Pharmaceutical Co., Ltd

Ironwood Pharmaceuticals, Inc.

Request free sample to get a complete analysis of top-performing companies @ https://www.millioninsights.com/industry-reports/gastroesophageal-reflux-disease-gerd-therapeutics-market/request-sample

Application Outlook:

Antacids

H2 Receptor Blockers

Proton Pump Inhibitors (PPIs)

Pro-kinetic agents

Regional Insights:

Browse Related Category Research Reports @ https://blog.naver.com/tomclark

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juniperpublisherscellscienc-blog · 5 years ago

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Development of Enpp1 Inhibitors as a Strategy to Activate Stimulator of Interferon Genes (STING) in Cancers and Other Diseases- Juniper Publishers

Abstract

Ecto-nucleotide pyrophosphatase/phosphodiesterase-1 (ENPP1/NPP1) is a membrane-bound nucleotide metabolizing enzyme that is implicated in a variety of physiological and pathological conditions. Recently, ENPP1 was discovered as the dominant 2’3’-cGAMP hydrolyzing enzyme. 2’3’-cGAMP is the endogenous STING agonist, generated from breakdown of cytosolic DNA by cGAS. Hydrolysis resistant 2’3’-cGAMP’s have been demonstrated to be potent activators of STING-dependent innate immunity and these are currently undergoing clinical trials in cancer. Here we discuss ENPP1 as a potential therapeutic target for activation of STING-dependent innate immune response.

Keywords: Innate immunity; STING; ENPP1/NPP1; Cytokines; Immunotherapies; Interferon; T-cell priming

Introduction

Innate immunity is the first response in the human body against pathogenic, or disease-causing stimuli. These stimuli can vary, and include viruses, perturbed normal tissue, and dying cancer cells. It is an important response, as it prevents continued proliferation of these pathogens and maintains a state of homeostasis within the body. It can also accommodate the development of a specific induced immune response during the first, or primary infection and, can therefore, establish inflammatory conditions. This induced response is specific because of the many different expressions that the cell surface gives off in the form of pattern recognition receptors, which can identify many of the molecules of life, such as, polysaccharides, glycoproteins, glycolipids, and nucleic acids [1].

The definition of innate immunity has altered over time. In earlier years, it was believed that innate immune response was premeditated. However, recent studies have shown that innate immunity is actually a specific response that results from damage or pathogen-associated molecular patterns (DAMP/PAMPs) [2]. In the initial phase, the innate immune system is able to coordinate inflammatory responses through cells of the hematopoietic compartment (neutrophils, macrophages and monocytes) and create conditions suitable for microbial clearance. In the second phase, other cells like dendritic cells are able to process antigens and present them on the surface in concert with major histocompatibility complex (MHC) to prime T-cells. This also allows the body to more effectively fight against infections of the same or similar type in the future. This “memory” is dependent on two specific types of cells: natural killer (NK) cells and macrophages. These cells provide crucial protection against reinfection in the immune system [3]. This “memory” found in innate immune systems is present in both vertebrate and invertebrate organisms.

Cytokines in Innate Immune Response

Cytokines are possibly the most indispensable component of the innate immune response. Cytokines are secreted by cells of the immune system and facilitate interaction between different types of cells. There are many different types of cytokines, and they are classified mainly by their biological functions. The main types of cytokines are: interferons (INFs), interleukins (ILs), transforming growth factors (TGFs), and tumor necrosis factors (TNFs) [4]. Interferons are the most commonly found type of cytokine in vertebrates and mammals and are crucial to mediate antiviral defense. To date, there have been three types of interferons discovered in vertebrates, and specifically mammals: Types 1, 2 and 3. Type 1 IFNs typically facilitate the antiviral response against microbial infection-causing pathogens. Type 2 IFNs also facilitate antiviral response, but at the same time, vitalize the process of phagocytosis and inhibit cell growth. Type 3 IFNs have been demonstrated to be strikingly similar in function to Type 1 IFNs [5,6]. Interleukins are a type of cytokines that also facilitate inflammatory responses in the immune system and help to stimulate cell growth [7]. Transforming growth factors (TGFs) regulate cell growth, help stimulate the growth of oocyte cells (which are found in the ovum), repair wounds inflicted upon the body, participate in immunosuppression, or reduce the activity of the immune system when naturally required [8]. Finally, tumor necrosis factors (TNFs) help to stimulate macrophages as they participate in the biological process of phagocytosis [9].

STING (Stimulator of interferon genes) as a DNA sensor

STING has been identified as a major signaling molecule that plays a pivotal role in innate immune response by inducing the production of interferons. STING is a cytoplasmic pattern recognition receptor activated by nucleic acid ligands known as cyclic dinucleotides (CDNs). These CDNs are generated by the DNA sensor cyclic GMP-AMP synthase (cGAS) using cytosolic DNA from extrinsic pathogens or endogenous aberrant self-DNA [10-12]. In case of tumors, it is probable that dying tumor cells are sources of dsDNA in the cytoplasm. In addition to CDN’s, STING can directly sense DNA and this dual sensing has been uncoupled with specific mutations in STING [10]. Activation of STING induces its binding with a kinase TBK1 (TANK-binding kinase 1) and further phosphorylation and dimerization of IRF3 (Interferon regulatory factor 3). IRF3 and another transcription factor that is activated by STING (STAT6) translocate to nucleus and bind to interferon promoters leading to production of type I interferons.

It is suggested that STING pathway is the main innate immune sensing pathway within tumor microenvironment and the main cell types in the tumor microenvironment that produce type I interferons are the dendritic cells [13,14]. In addition to the activation of STING pathway in response to tumor-derived DNA, dendritic cells prime T-cells by presenting tumor- associated antigens. These effects then create a signaling pathway, which allows T-cells, a main feature of the active immune response, to neutralize tumor cells [15,16]. Some tumor cells are able to “disguise” themselves to the innate immune response by upregulating immune checkpoints, or by having a lack of innate immune response within the tumor. A recent study reported that STING is epigenetically silenced in some cancers [17]. Additionally, oncoproteins from viruses such as human papillomavirus can bind and block activation of STING [18]. Thus, a cytosolic DNA sensing pathway is important for activation of innate immune response. In recent years, there has been considerable interest in the field of immune-oncology as well as an increase in the number of immunotherapies available [19,20].

ENPP1(Ectonucleotide Pyrophosphatase/Phosphodiesterase- 1) And Its Role in Innate Immunity

ENPP1 is a membrane bound enzyme that is an important regulator of extracellular inorganic pyrophosphate in osteoblasts and chondrocytes [21]. It is essential for prevention of soft tissue mineralization and ENPP1 deficient mice can have abnormal gait and progressive calcification in ectopic sites [22]. ENPP1 is responsible for hydrolysis of extracellular nucleotide triphosphates to produce inorganic pyrophosphates (PPi) [23]. Recent investigations have shown that ENPP1 plays a much larger role in limiting the innate immune response of the human body. It has been discovered that STING pathway is regulated by ENPP1[24]. ENPP1 was identified as the major hydrolase for the most potent endogenous CDN ligand for STING: 2’3’-cGAMP [25]. Importantly, it was demonstrated that denaturation of 2’3’-cGAMP can control the activation of the STING pathway [26]. Phosphothioate analogs of 2’3’-cGAMP resistant to ENPP1- mediated hydrolysis potently activate STING [25] and mediate anti-tumor responses. These analogs have now entered clinical trials as intra-tumoral injections in various advance cancers (Figure 1).

In another study, it was shown that Mycobacterium tuberculosis evades host immune response through a bacterial phosphodiesterase (CdnP) which inactivates host 2’3’-cGAMP. Loss of ENPP1 attenuated Mycobacterium tuberculosis infection, as did the inhibition of CdnP, the phosphodiesterase of Mycobacterium tuberculosis [27] More recently, inactivation of porcine ENPP1 was shown to attenuate pseudorabies infection through an interferon-β dependent response [28]. Many viruses generate antagonist proteins that can inactivate cGAS-STING pathway [29]. ENPP1 is differentially expressed in immune cells with low levels in NK cells, DC and macrophages and high levels in neutrophils [30]. ENPP1 is also expressed in a small subset of B-cells and studies suggest that these cells may be involved in modulation of T-cell activity [31]. Interestingly, ENPP1 expression was reported to be elevated in the M2 subtype of macrophages that are known to play a role in tumor promotion [28,32,33]. Other studies have indicated that expression of ENPP1 is increased in astrocytic tumors, breast cancers, and head and neck cancers [34-36]. Thus, inhibition of ENPP1 in humans may provide opportunities for treatment of cancers and pathogenic infections.

Challenges in Development of Inhibitors of ENPP1 for Human Use

Given the various functions for ENPP1 in regulating host immune responses, there is interest in development of ENPP1 inhibitors for human use. These inhibitors may have promising activity in human cancers and infectious pathologies. There are various practical challenges in development of these inhibitors. ENPP1 is a type II transmembrane glycoprotein that belongs to a family of ectonucleotide pyrophosphatase/phosphodiesterase (Enpp) family and consist of seven distinct proteins with distinct functions [37]. Thus, any inhibitor strategy will have to consider development challenges for specificity. In the published crystal structure of mouse ENPP1, there are important structural differences between ENPP2 and ENPP1. The N-terminal somatomedin-like (SMB) domains of ENPP1 do not interact with catalytic domains unlike those in ENPP2 [38,39]. ENPP1 appears to lack a hydrophobic pocket in contrast to ENPP2 although interdomain interactions are preserved [37-40]. Despite these challenges, our group and others have described novel selective and orally bioavailable inhibitors of ENPP1 [41-45].

Fundamental effects of ENPP1 inhibition on host immune response are still being determined. It is not known, for instance, if ENPP1 deficiency in mouse models impairs anti-tumor growth. Thus, optimal duration and intensity of ENPP1 inhibition is still being developed. This is important since systemic administration of these inhibitors can cause unwanted side effects due to excessive release of interferons. Interestingly, ENPP1 knockout mice are viable, thus pointing to possible avenues for development of such inhibitors. Prolonged administration of ENPP1 inhibitors may lead to unwanted effects on bony tissues and ectopic calcifications although this has been disputed in various studies in literature [46]. This is because bone and cartilage effects may not be entirely mediated by ENPP1. In other studies, oral administration of pyrophosphate can attenuate the connective tissue calcifications mediated by ENPP1 mutations in mouse models [47].

Conclusion

As hyper-activation of STING pathway may lead to production of abnormally high levels of proinflammatory cytokines, it is necessary to develop therapeutics that target STING pathway indirectly. Inhibition of ENPP1 activity is one approach that may result in optimal activation of STING pathway, enough to have anti-tumor effects, and minimize unintended consequences. Given the role of ENPP1 in immune modulation and tumor promotion, there is an increased interest to develop novel therapies based on inhibition of the ENPP1 activity and this will emerge as an interesting area in the coming years.

Acknowledgments

We thank Dr. Hariprasad Vankayalapati for advice in developing this review.

https://juniperpublishers.com/ijcsmb/IJCSMB.MS.ID.555655.php

For more Open access journals please visit our site: Juniper Publishers

For more articles please click on Journal of Cell Science & Molecular Biology

#Cell Science #Molecular biology #Stem cells #Open access journals #Juniper Publishers

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mysticalpeacenut · 3 months ago

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How Biomolecular Interactions Drive Innovation

Biomolecular interactions lie on the coronary heart of almost every biological method that occurs inside living organisms. From cell verbal exchange and protein folding to gene expression and immune responses, these interactions govern the complex dance of lifestyles on a molecular level. Understanding and leveraging these interactions is driving a brand new wave of innovation in biotechnology, drug discovery, and therapeutic improvement.

This blog explores how biomolecular interactions, which includes the superior Magna™ Biomolecular Interactions generation, are fueling scientific breakthroughs and transforming the destiny of medication.

The Fundamentals of Biomolecular Interactions

At their center, biomolecular interactions talk to the methods wherein different molecules-along with proteins, nucleic acids, lipids, and small molecules-have interaction with every different to perform organic functions. These interactions are incredibly specific and involve non-covalent forces inclusive of hydrogen bonding, ionic interactions, hydrophobic effects, and van der Waals forces.

Key kinds of biomolecular interactions include:

Protein-Protein Interactions (PPIs): These are vital for in reality each factor of mobile function, along with cell signaling, metabolism, and immune responses.

Protein-DNA/RNA Interactions: Central to processes like gene expression and regulation, these interactions manage how genetic information is transcribed and translated.

Enzyme-Substrate Interactions: These power catalytic reactions, important for metabolic pathways, and other biochemical strategies.

Understanding those molecular interactions offers scientists insights into how illnesses increase and development, leading to modern healing strategies that can intervene at the molecular degree.

Unlocking Potential Through Molecular Interactions

As our expertise of molecular interactions deepens, the potential for brand new programs in remedy and biotechnology grows exponentially. Researchers at the moment are capable of layout capsules and remedies that particularly goal key biomolecules, allowing greater precise remedy techniques with fewer side results.

One of the most promising regions of innovation lies within the manipulation of molecular interactions to expand focused healing procedures. For instance, researchers have recognized specific protein-protein interactions that make contributions to cancer development, which has brought about the improvement of medicine that disrupt those interactions, halting tumor growth.

In addition to drug discovery, the look at of biomolecular interactions is transforming fields like synthetic biology, personalized remedy, and diagnostics. By engineering molecules that engage in unique approaches, scientists are growing new biomolecular equipment for gene modifying, ailment modeling, and greater.

Magna™ Biomolecular Interactions: A Technological Leap

Among the maximum exciting advancements on this area is Magna™ Biomolecular Interactions, a modern-day era advanced by means of Depixus. This step forward technology permits researchers to precisely have a look at the interactions between biomolecules, supplying unheard of detail and accuracy.

Magna™ generation makes use of superior methods to seize and analyze how unique biomolecules engage in actual time. This facts can be used to are expecting how proteins will behave in one-of-a-kind environments, how small molecules can also bind to target proteins, or how genetic fabric may additionally engage with regulatory proteins. The capability to reveal these interactions at this kind of granular stage opens up new opportunities for drug improvement and customized remedies.

For instance, in RNA-focused drug discovery, information the right interactions between RNA molecules and therapeutic compounds is essential. Magna™ Biomolecular Interactions allows scientists to explore these interactions in great detail, helping to increase RNA-centered capsules with extra efficacy and specificity.

Biomolecular Interactions in Drug Discovery

The role of biomolecular interactions in drug discovery cannot be overstated. Modern drug layout frequently hinges on the identity of important molecular interactions that make a contribution to disease. By concentrated on these interactions, scientists can expand treatment plans that interfere on the earliest levels of disorder progression.

For example, in illnesses like Alzheimer's, most cancers, and autoimmune disorders, sure biomolecular interactions can pressure the disease technique. By inhibiting or enhancing those interactions, researchers can create remedies that particularly address the underlying reasons of the sickness, instead of simply treating the signs and symptoms.

This focused technique to drug discovery is mainly relevant inside the technology of personalized medication, in which treatments may be tailor-made to an man or woman's specific molecular profile. The ability to examine molecular interactions at a extraordinarily unique degree, made possible with the aid of innovations like Magna™ technology, is paving the way for extra effective and customized healing options.

The Future of Innovation

The destiny of innovation in biotechnology and medicinal drug is being shaped by our increasing potential to apprehend and manipulate biomolecular interactions. As equipment like Magna™ Biomolecular Interactions hold to adapt, we can expect even extra advancements in the observe of molecular processes, leading to new discoveries so as to trade the manner we approach disorder remedy and prevention.

This generation holds promise no longer handiest for drug discovery however additionally for regions along with artificial biology, where engineered biomolecular interactions can be used to create new biological systems with custom designed capabilities. The capability programs are significant and sundry, from growing novel gene healing procedures to developing biosensors that stumble on sickness markers at an early level.

Conclusion

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Reposted Blog Post URL: https://petrickzagblogger.wordpress.com/2024/08/20/biomolecular-interactions-drive-innovation/

#Biomolecular Interactions #Molecular Interactions #Magna™ Biomolecular Interactions #depixustechnology

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celiacandthebeast · 7 years ago

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News Briefs

Digestive Disease Week (DDW), the annual convention of gastroenterologists and other medical specialists, was held this year in Chicago in May. Here are some highlights of the research presented there.

Celiac Testing Methods

Many people start a gluten-free diet before they’re officially tested for celiac disease. This can later skew an accurate diagnosis, as a patient must be consuming gluten for celiac blood tests to be effective. Researchers from ImmusanT, a lab that’s working to develop the Nexvax2 vaccine for celiac disease, looked at changes in circulating levels of cytokines (proteins secreted by specific immune cells) in celiac disease volunteers on a gluten-free diet. They found that when these individuals consumed gluten, they showed elevated levels of IL-2 and IL-8 cytokines within two to four hours after ingestion. Measurement of these cytokines following a gluten challenge may help identify celiac disease in those already on a gluten-free diet, the researchers said.

Antibody blood tests, such as the tTG test, are often poor predictors of intestinal healing in those with celiac disease. About a third of celiac patients with normal antibody test results actually show tissue damage on a biopsy. Researchers at the Mayo Clinic reported that combining antibody blood tests (tTG and DGP) with tests for intestinal fatty acid binding proteins (I-FABP), a marker of mucosal damage, can be useful in assessing intestinal healing in cases where celiac disease antibody tests are only moderately elevated.

Doctors find it difficult to assess their celiac patients’ true adherence to the gluten-free diet. Argentinian researchers reported that gluten immunogenic peptides (GIP) detected in stool and urine may help physicians identify whether patients have consumed gluten within 48 to 72 hours after ingestion. These tests could be used in conjunction with other tests to assess whether a patient is inadvertently consuming gluten.

Celiac & Associated Conditions

Researchers in Dublin looked into the co-existence of other immune-mediated conditions in people with celiac disease. They found that about 30 percent of celiacs are likely to have an additional autoimmune condition. The most prevalent are thyroid disease (almost 64 percent), type 1 diabetes (about 12 percent), psoriasis (almost 9 percent), inflammatory bowel disease (6 percent) and rheumatoid arthritis (5 percent).

Researchers at the Mayo Clinic looked at gender-based differences in people with celiac disease, including the rate of associated autoimmune diseases. Their study examined stored serum from a community-based sample of people age 18 to 49 living in a Minnesota county. Concurrent autoimmune diseases were recorded in almost 20 percent of the females and almost 25 percent of the males. Depression was more than twice as common in females (almost 28 percent) than males (about 10 percent).

Persistent Villous Atrophy

Some celiac patients continue to have symptoms and intestinal villous atrophy despite being on a gluten-free diet. A multi-site study looked into the causes and found that, in a small percentage of people, villous atrophy was associated with use of proton-pump inhibitors (PPIs, a type of reflux medication), non-steroidal anti-inflammatory drugs (NSAIDs) or selective serotonin reuptake inhibitors (SSRIs, a type of antidepressant medication). Researchers concluded that the majority of symptomatic celiacs in the study did not have active disease. They recommended further study on the impact of PPIs, NSAIDs and SSRIs on mucosal healing in celiac disease.

In separate presentations at DDW, various researchers pointed to other factors that can contribute to ongoing villous atrophy, including rotavirus, HIV infection, cow’s milk protein enteropathy, certain medications (such as olmesartan, a blood pressure medicine), giardiasis (a parasitic infection), Crohn’s disease, H. pylori infection and bacterial overgrowth.

ATIs in Wheat

Many people with non-celiac gluten sensitivity may actually be reacting to other components in wheat, not to gluten. A multi-site study examined amylase trypsin inhibitors (ATIs, pest-resistant molecules that play a role in grain maturation) and found that ATIs in wheat can initiate innate immunity in celiac disease and promote symptoms in those with non-celiac wheat sensitivity.

In a separate study, some of these researchers identified and tested bacterial strains with a capacity to degrade ATIs and reduce their immune stimulatory activity. They found that certain Lactobacillusstrains have the capacity to change the inflammatory effects of ATIs. Supplementation with these Lactobacillus strains may help gluten- and wheat-related disorders, they concluded. More research is needed.

Quality of Life

Various studies at DDW examined quality-of-life indicators for those with celiac disease on the gluten-free diet. Research presented by the Celiac Disease Center at Columbia University revealed that the cost of gluten-free products is 183 percent more expensive than their wheat-based counterparts. Researchers reported that availability of gluten-free products in traditional grocery stores has increased, while online availability has dropped.

Another study from Columbia University showed that almost half (46 percent) of patients with biopsy-diagnosed celiac disease have a positive depression screen. Researchers found a moderate correlation between more severe celiac disease symptoms and depression. They recommended that physicians consider depression screening for their patients with persistent celiac symptoms.

Researchers from Columbia University also found that celiac teens and adults with the highest adherence to the gluten-free diet had significantly lower quality-of-life scores than those with the lowest adherence. Roughly a third of individuals with celiac disease had dysphoria (unhappiness, dissatisfaction) stemming from worry about cross-contamination (adults 28 percent, teens 37 percent), dislike of being so vigilant and asking constant questions about their food (adults 28 percent, teens 27 percent), distrust of restaurant menus leading to extensive planning (adults 36 percent, teens 30 percent), and constant educating of uninformed or dismissive waiters (adults 26 percent, teens 20 percent). Researchers concluded that hypervigilance can have an adverse effect on quality of life.

“Research is needed to determine the best level of dietary adherence that can both avoid intestinal damage and long-term complications, yet maximize quality of life and energy levels,” they wrote.

#celiac #celiac disease #gluten #gluten free

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