#drug development

[unbfacts]

[cbirt]

A team of researchers from the University of Chinese Academy of Sciences, China, and collaborators developed GeneCompass, one of the first foundation models of its kind that encompasses a vast expanse of knowledge across a diverse array of species, owing to the fact that it has been trained on over 120 million single-cell transcriptomes derived from the genomes of mice and humans. It is a self-supervised model. During the process of pre-training the model, it retrieves information from four types of biological datasets in the form of ‘prior knowledge’ and integrates it. It has excelled and outperformed several state-of-the-art models when studying a single species. It can also open new avenues for carrying out studies across different combinations of species other than humans and mice. This model can potentially contribute to discovering key regulators that determine cell fate and to identifying promising target candidates in the drug discovery and development field.

It is essential to decode universal regulatory mechanisms that dictate the expression of genes across a diverse set of organisms for accelerating clinical research and expanding our existing knowledge of basic and crucial life processes. Traditional research methodologies and existing deep-learning models have only considered using individual models of organisms separately. This has resulted in a dearth of integrated knowledge of features observed across different cell types over a variety of species. The development of this model was made possible by combining the outcomes of recent advancements in the fields of deep-learning (DL) methods and single-cell sequencing methods.

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[scientificinquirer-blog]

DAILY DOSE: Hurricane Beryl Nears Grenada as Category 4 Threat; Moderna Seeks FDA Nod for Dual COVID-Flu Shot.

HURRICANE BERYL INTENSIFIES, MENACES ISLANDS WITH CATASTROPHIC IMPACT Hurricane Beryl escalated to a Category 4 storm as it moved through the Windward Islands, threatening communities with severe storm surge, destructive winds, and flash flooding. Particularly at risk were St. Vincent, the Grenadines, and Grenada, with Beryl positioned 70 miles east of Grenada, featuring 130 mph winds. While a…

[sanguinifex]

This is huge. As of 8/30/2023, the Federal Department of Health and Human Services wants the DEA to reclassify from schedule 1 (no medical use, completely verboten) to schedule 3 (widely accepted medical use, some abuse potential, similar to Tylenol 3).

It won’t just allow doctors to prescribe it and reduce the penalties for having it if you’re not “supposed to”; it’ll also make it much easier for researchers to do studies with it, giving us health data that is currently lacking. For example, we don’t know much about how THC and CBD affect the liver or liver enzyme levels except in end stage liver disease patients, and what data we do have is decades old and of poor to middling quality.

The expansion of research a Schedule 3 reclassification would allow could pave the way for a safe, non-addictive pain medication based on cannabinoids that works primarily on the CB2 receptors and either doesn’t pass the blood-brain barrier or does cross it but doesn’t cause euphoria or sedation in most patients. In other words, the holy grail of pain medicine. Currently, the only painkiller that utilizes the endocannabinoid system is acetaminophen (Tylenol), which is a weak reuptake inhibitor of anandamide but primarily works via the prostaglandin system, and which is also highly hepatotoxic and somewhat nephrotoxic, and which probably wouldn’t be approved except as prescription fever and pain management, the latter primarily as an adjuvant to opiates, if it were a new drug being reviewed by the FDA today.

This is a really big example of how both parties are not the same. A Republican administration DHHS wouldn’t do this. If the No Fun Allowed Agency follows instructions, this opens up a lot of possibilities for a lot of people. It also completely bypasses the partisan legislatures and courts. Technically it’s easier for a future administration to overturn, but historically the DEA rarely reschedules medications without strong external pressure. (And in this case, it’s already functionally legal for those 21+ in most of the country anyway.)

[intrinsequehealth]

Intrinseque Health - Clinical Supply Chain We Build and Execute Complex Clinical Supply Plans

Intrinseque Health is an EN ISO 13485 Certified Global clinical trial support services provider committed to the utmost in service delivery to drug development organizations (Pharmaceutical, Biotechnology, Medical Device & Contract Research Organizations (CROs)). Our team of industry professionals has over 300 years of combined experience supporting global clinical trials across a wide array of therapeutic areas. This vast experience enables us to empathize with our Customers while providing best-in-class solutions to overcome the hurdles and pain-points of conducting a clinical trial.

Regions & countries throughout the world will often present a unique set of regulatory and logistical challenges. It is our responsibility to understand and overcome these while ensuring that your products, supplies, equipment and services are available where needed to ensure study timelines are met. Intrinseque Health utilizes an operational methodology that is based on proven, cost-effective clinical supply chain strategy for each clinical trial. Our practice is to engage with our customers, early and often to ensure implementation of a robust clinical supply plan, resulting in the most successful study start-up and initiation.

[happy-smile-flowers]

Salt formation: an effective means to improve the physical and chemical properties of drug molecules and enhance the druggability of drugs

In drug development, drug forming research, including pharmacodynamics, pharmacokinetics, and early safety evaluation of drugs, is required to determine whether the active compound has the potential to be developed into a pill. The drug-forming properties of drugs are also an essential part of the drug-forming evaluation, and salt formation is one of the effective means to improve the physicochemical properties of drug molecules and enhance drug-forming properties.

Many drugs are salts of organic acids or bases. The salt formation can make some oily organic acids or organic bases solid, which is conducive to preparing concrete dosage forms. Moreover, the salt formation of drugs increases the water solubility, which is conducive to preparing some aqueous dosage forms, such as water injection and oral liquid. The salt formation process is often a purification process, which removes the impurities mixed in the drug that cannot become salt, etc. So what are the benefits of salt formation in drug development studies?

1,Salt formation of drugs can change the solubility of drugs and improve drug-forming properties

The solubility of drugs affects their pharmacokinetic properties, chemical stability, and the choice of dosage form, which is an essential element in evaluating drug-forming properties. A salt formation can change the solubility of drugs and improve the water solubility of drugs through salt formation, which is the primary method to develop intravenous injections of drugs, such as the poor water solubility of diuretic etanercept, which is mainly available in tablet form.

Still, its sodium salt has better water solubility and can be used to prepare intravenous injections. The free base of the antipsychotic haloperidol is also marketed mainly as a tablet due to its low solubility. At the same time, its lactate can be used to prepare injectable solutions with improved solubility.

Sometimes it is necessary to prepare extended-release dosage forms by reducing the solubility of the drug. In this case, it is required to form a salt of the drug with an acid or base of higher relative molecular mass and hydrophobicity. For example, the commercially available dosage forms of antidepressant trazodone hydrochloride are tablets, oral solutions, etc. The study of trazodone in salt found that its p-toluenesulfonate and dihydroxynaphthalate are much less soluble in water than sulfate, and hydrochloride p-toluenesulfonate is more suitable for the preparation of slow-release oral formulation.

2,Salt formation can improve drug stability

Formulation evaluation also needs to rely more on data generated from pre-prescription research work, such as extreme pH, high temperature, freeze-thaw, light, forced oxidation, and other forced degradation experiments to understand the stability of drugs. Medicilon offers a full suite of chemical drug development services integrated from start to finish. We provide a one-stop service through pre-prescription studies, drug analysis, drug stability studies, formulation development, and complete CMC services.

The stability of the drug is directly related to its dosage form and the selection of production and packaging conditions, and it even affects the effect of the final preparation. Some researchers chose the insoluble phenazopyridine (PAP) as a model drug and improved the solubility and stability of phenazopyridine through drug co-crystals and salts.

The marketed product of phenazopyridine is phenazopyridine hydrochloride. Still, the peak plasma concentration in rats is only 10-20 ng after 200 mg dose administration, and it is for these reasons that the clinical application of PAP is limited. Therefore, the investigators prepared one eutectic formed by phenazopyridine with phthalimide (1) and two salts with 4-hydroxyphenyl acetic acid (2) and saccharin (3) by solution method and spiked grinding method, respectively, and their structures obtained by X-ray single crystal diffraction showed the presence of hydrogen bonding between phenazopyridine and all three eutectic ligands, collectively called hydrogen bonding complexes [1].

X-ray powder diffraction, DSC, and IR characterized it. The powder solubility of the three hydrogen-bonded complexes was measured, and the hygroscopicity of the solid powders was examined at 85% and 98% relative humidity for 1, 3, 5, 7, 10, 14, 21, and 28 days. The experimental results showed that the melting points of the three hydrogen-bonded complexes were all between phenazopyridine and eutectic ligands; the powder solubility of 1-3 was 10, 7.5, and 2 times that of PAP, respectively; the hygroscopicity was much lower than that of PAP and its hydrochloride under the conditions of 85% and 98% relative humidity. According to the above results, it is clear that 1-3 has a good prospect for improving the bioavailability and stability of phenazopyridine.

3,Salt formation can change drug compliance

Drug formulation should be safe, effective, stable, and easy for patients to accept, i.e., good compliance. An essential indicator of compliance with oral formulations is the acceptability of taste, which is particularly important when the drug is administered in liquid, chewable, or effervescent dosage forms. For example, the prerequisite for oral drugs to produce a taste response must first be dissolved in the mouth or taken in solution. Therefore, one of the ways to reduce the bitterness of orally administered drugs is to make them into poorly soluble salts and to make their saturated concentration below the threshold for producing taste sensation.

4,Into salt, can extend the patent protection of the drug or circumvent its patent protection

In the R&D process of new drugs, once an active compound is discovered, it is generally applied for a patent on its chemical structure to ensure the novelty of the patent. After the drug is marketed, the developer will further develop its derivatives, such as making salts or changing the crystal form and dosage form, and file subsequent patent applications to obtain the longest possible patent protection period. Nowadays, most new drugs marketed internationally use this type of patent protection.

In addition, drug salting can reduce adverse effects. In developing salt-forming drugs, the key is to select the acid or base with which the drug is salted. The selection of the acid or base should consider its pKa value and safety, as well as the route of administration and dosage form after salting. In conclusion, drug-forming studies and drug-forming evaluations can be conducted to determine the drug-forming properties of drugs better and improve the efficiency of new drug development.

[1] Improvement of solubility and stability of phenazopyridine by drug eutectic and salt [J]

[sbgridconsortium]

Ligand and G-protein selectivity in the κ-opioid receptor

The dark history of opioids use in pain management is a testament to the complexity that comes with discovering potential drug targets in the brain. The therapeutic target of opioids is usually the μ-opioid receptor (MOR). This interaction between the MOR and opioids creates the sensation of pain relief by the downstream signaling of the MOR through the Gi/o-family proteins. Sadly, MOR has downstream effects that can cause outcomes other than diminishing pain, like addiction and abuse. 

For this reason, other viable targets for pain management are important in trying to lessen dependence on opioids. One way to lessen the unintended consequences of opioids while still effectively managing pain is to target pathways relevant to pain relief downstream of the MOR while avoiding pathways that cause other effects. One possible target could be the κ-opioid receptor (KOR). This receptor targets similar downstream effects responsible for the pain reducing effects of the MOR, while not causing the similar levels of addiction. The KOR does however, tend to cause hallucinogenic symptoms when targeted. 

Above: Published structure of KOR bound to Gg protein. PDB: 8DZR. CC BY SBGRID

To provide insight on this effect, SBGrid member Tao Che and collaborators studied how ligand binding to KOR affects its signaling machinery, the Gi/o-family proteins. Using cryo-EM, they studied the specificity of the KOR to ligands and the selectivity of four types of Gi/o-family proteins to the KOR/ligand complexes. From these structures the authors are able to determine a high level of selectivity of KOR to specific ligands and high levels of selectivity of G proteins to KOR/ligand complexes. The specificity of certain Gi/o-family proteins to certain KOR/ligand complexes could suggest that therapeutics can be designed to not only target the KOR, but also select desired downstream pathways by signaling through specific Gi/o-family proteins.

Read more about this work in Nature.

-Vida Storm Robertson, Fisk University

[white-throated-packrat]

In the USA, the first tests done in humans are Phase I Clinical Trials, and all they test is *safety*. This is after all the pre-clinical testing, which are done in the simplest animal that they can be done in -- for drugs intended for eventual human use, that is usually lab mice but sometimes rabbits.

Phase I trials are when you give microdoses of your drug to healthy volunteers who do not have the target disease/disorder just to see if a healthy person can tolerate it.

When you don't have to test for safety first, you get things like the Elixir Sulfanilamide Disaster of 1937, which was a mass poisoning incident because at the time drug didn't have to be tested for safety before being put on the market.

The US Food, Drugs, and Cosmetics Act of 1938 was a direct result of the Elixir Sulfanilamide Disaster. It's protected Americans (and anyone who uses drugs developed or exported by America) for almot 90 years.

Let's hope the current chaos in the US federal government is squelched quickly before it destroys the FDA (Food and Drug Administration).

the cognitive dissonance from people who want the products of modern medicine but get weird about animal research. like im sorry but this is necessary for the survival of the society we currently live in. and the scientists who work on these things are not evil cackling psychopaths. anyone you talk to in animal research has incredibly complex feelings about their work and incredibly complex relationships to the animals in their care. there are regulations and oversight and penalties in place to make the work as humane as possible and scientists are overwhelmingly the ones enforcing and advocating for better care.

[lordsmerchantco]

The Future of Pharmaceutical Companies: Innovations, Trends, and Consumer Insights

Table of Contents Introduction The Role of AI in Pharmaceuticals Key Trends Shaping the Industry How to Choose the Right Pharmaceutical Products AI Overview: Smart Drug Discovery and Development Featured Snippets & AEO Optimization for Pharma GEO Targeting for Local and Global Reach FAQs About Pharmaceutical Industry People Also Ask (PAA) People Also Search (PAS) Case Studies:…

[cbirt]

A team of researchers at the University of California, San Diego, came together to develop a chatbot specifically catered to drug discovery called DrugChat. It is similar to ChatGPT on the basis that users can give question prompts to the model on any drug compound under study after uploading the drug’s molecular graph and can get answers to their queries in an interactive and iterative manner. It is composed of a graph neural network (GNN), a large language model (LLM), and an adaptor.

Traditional methods of drug discovery, which have been carried out experimentally, have been expensive and time-consuming. Approval for even a single drug to go up in pharmaceutical stores for sale takes several years and a lot of money. Experimental methods also require a lot of labor and step-by-step testing, often ending up in failure at the last few stages of drug development. Taking advantage of artificial intelligence (AI) to mitigate these issues is crucial in today’s fast-paced and demanding world, where novel drugs are needed to treat an ever-increasing list of diseases.

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[scientificinquirer-blog]

Scientists Say NIH Officials Told Them To Scrub mRNA References on Grants

National Institutes of Health officials have urged scientists to remove all references to mRNA vaccine technology from their grant applications, two researchers said, in a move that signaled the agency might abandon a promising field of medical research. The mRNA technology is under study at the NIH for prevention and treatment of infectious diseases, including flu and AIDS, and also cancer. It…

[neosciencehub]

The Role of Gene Diversity in Personalized Medicine

The Role of Gene Diversity in Personalized Medicine @neosciencehub #GeneDiversity #PersonalizedMedicine #Diseasesusceptibility #neosciencehub

In recent years, the field of genetics has gained significant traction, particularly in understanding how genetic diversity among populations can influence health, disease susceptibility, and treatment responses. A landmark study known as the Genome India project, initiated in 2020, has been pivotal in uncovering the complexities of the Indian gene pool, which is considered one of the most…

[sanguinifex]

Naked mole rats don’t just survive via using fructose to bypass oxygen. They also got rid of the kind of pain that doesn’t mean “immediate danger.”

Imagine getting a viral vector gene therapy that turns off fibromyalgia. I, for one, am looking forward to that future.

[mukeshmourya016]

Popular Clinical Operations at Clinfinite Solutions

Introduction:

Doctors and researchers are always working hard to find new ways to treat diseases and help people stay healthy. But before new treatments can be given to patients, they must be carefully tested. This testing is done through clinical studies, where doctors and scientists test new medicines or treatments to make sure they are safe. Running these studies and organizing the testing process is known as clinical operations. Clinical operations make sure everything in a study is done correctly so that the researchers get the right answers.

What is Clinical Operations?

Clinical operations is the process of managing and organizing clinical trials, which are studies that test new medicines or treatments. These studies help doctors learn if a new treatment is safe and works well for patients. Clinical operations involve many different steps. First, researchers need to find people who want to take part in the study. Then, they need to make sure that the study follows the rules and that everyone is safe during the trial. Clinical operations also include making sure the right data is collected, that tests are done correctly, and that everything happens on time.

Clinfinite Solutions helps with all of these tasks. They make sure the clinical trials are set up properly, that all the steps are followed, and that the data collected during the trial is accurate. This is important because the data is what doctors use to decide if a treatment is safe and effective. If the data is wrong, it could lead to mistakes in medical care.

Importance of Clinical Operations:

Clinical operations are very important because they help ensure that clinical studies are done the right way. If a clinical study is not managed well, it can lead to mistakes that might harm people or cause researchers to get the wrong answers. For example, if the study is not run on time or if the wrong people are included, the results may not be correct. This is why clinical operations are essential – they make sure everything is done carefully, so researchers can trust the results.

Another important reason clinical operations are important is that they help speed up the process of finding new treatments. Clinical studies can take a long time to complete, but by having strong clinical operations in place, researchers can complete the studies faster and with more accuracy. This helps doctors find new medicines and treatments that can help people get better more quickly.

Role of Clinfinite Solutions in Clinical Operations:

Clinfinite Solutions plays a very important role in clinical operations. They help manage many parts of the clinical study process, from planning the study to collecting and analyzing the data. One of the main roles of Clinfinite Solutions is to make sure that everything in the clinical trial is organized correctly. They help with finding the right people to join the study, making sure that the trial follows all the necessary rules, and making sure the study runs smoothly from beginning to end.

Clinfinite Solutions also helps collect the data from the clinical trial. In clinical studies, it is very important to collect accurate information. This can include details about how the treatment works if the person feels better, and if there are any side effects. Clinfinite Solutions helps ensure that this data is collected properly and stored safely. They also help keep track of any changes during the study, like when patients need to stop or start a new treatment.

Conclusion:

 In conclusion, clinical operations are a very important part of the medical research process. They help make sure that clinical studies are run safely, accurately, and efficiently. Without good clinical operations, researchers wouldn’t be able to trust the results of their studies, and new treatments might not be as safe or effective as they should be.

Clinfinite Solutions plays a key role in clinical operations by managing the studies, ensuring everything is organized properly, and collecting and analyzing data. They help doctors and researchers follow the rules and make sure everything is done safely. Their work is essential for helping new treatments and medicines reach patients and improve health.

[clinfinite123solution]

Pharmaceutical CRO: Transforming Drug Development with Clinfinite Solutions

The Pharmaceutical business is a unique field set apart by steady development and the quest for notable treatments. Notwithstanding, the excursion from exploration to showcase endorsement for new medications or clinical gadgets is complex, tedious, and asset serious. A Pharmaceutical Understanding Investigation Affiliation (CRO) like Clinfinite Game Plans is imperative in defeating this issue, enabling Drug and biotech associations to make their things available for purchase to the public beneficially and effectively.

What is a Pharmaceutical CRO?

A Pharmaceutical CRO is an affiliation acquiring pragmatic involvement by offering re-appropriated organizations that cover the entire prescription improvement process. These organizations consolidate preclinical investigation, clinical fundamentals, managerial sections, data on the board, and post-displaying studies. By cooperating with a CRO, Pharmaceutical associations can accelerate improvement courses of occasions, smooth out resources, and stay aware of consistency with managerial rules.

The Role of Clinfinite Solutions as a Leading Pharmaceutical CRO

At Clinfinite Solutions, we value being a confided-in accomplice for Pharmaceutical organizations around the world. Our aptitude traverses each part of medication advancement, guaranteeing that your undertakings are taken care of with the greatest possible level of amazing skill and accuracy.

Key Services Offered by Clinfinite Solutions

Preclinical Innovative work

Preclinical investigations are the underpinning of medication advancement. Clinfinite Solutions conducts extensive well-being and adequacy testing in consistency with administrative rules, empowering smooth changes to clinical stages.

Clinical Preliminary Administration

Our group oversees clinical preliminaries from Stage I through Stage IV, guaranteeing moral direction, exact information assortment, and vigorous preliminary execution. We handle patient enlistment, site checking, and convention adherence, giving start-to-finish preliminary administration arrangements.

Administrative Issues and Consistency

Exploring the complex administrative scene is fundamental for endorsement. Clinfinite Solutions offers master support in getting ready and submitting administrative archives, meeting the necessities of worldwide wellbeing specialists.

Information The board and Biostatistics

With state-of-the-art innovation and ability in biostatistics, we guarantee precise information examination and detailing. Our information the executive administrations guarantee the uprightness and dependability of preliminary outcomes.

Pharmacovigilance and Security Observing

Patient security is our first concern. We give complete pharmacovigilance administrations, including unfavorable occasion observing, risk appraisals, and security revealing, guaranteeing consistency with administrative orders.

Clinical Composition and Logical Documentation

Our accomplished clinical journalists plan great records, for example, concentrate on conventions, clinical review reports, and specialist pamphlets, customized to meet explicit administrative prerequisites.

Benefits of Partnering with Clinfinite Solutions

Sped up Advancement Courses of events

With our ability and smooth-out processes, we decrease time-to-advertise, empowering Pharmaceutical organizations to present treatments quicker.

Cost Streamlining

Re-appropriating clinical examination to Clinfinite Solutions dispenses with the requirement for a broad in-house framework, decreasing functional expenses fundamentally.

Worldwide Reach

Clinfinite Solutions has a presence across different districts, working with worldwide preliminaries and guaranteeing consistency with assorted administrative necessities.

Redone Arrangements

Every client is novel, and we configure customized techniques that take care of their particular objectives, guaranteeing a good outcome at each transformative phase.

Admittance to Ability

Our multidisciplinary group comprises of experienced experts in clinical examination, administrative undertakings, pharmacovigilance, and information the executives.

The Importance of Pharmaceutical CROs in Drug Development

The excursion of medication improvement includes a few phases, each introducing extraordinary difficulties. Pharmaceutical CROs address these difficulties successfully, offering important help:

Complex Preliminary Plans

Current clinical preliminaries frequently include imaginative plans and high-level approaches. CROs acquire skills in preliminary preparation, execution, and versatile plans.

Administrative Consistency

Every nation has its own administrative rules, making consistency an overwhelming errand. CROs like Clinfinite Solutions guarantee a smooth route through the administrative cycle.

Mechanical Incorporation

By utilizing cutting-edge innovations like man-made consciousness (computer-based intelligence), AI (ML), and electronic information catch (EDC), CROs improve preliminary proficiency and information precision.

Adaptability

Pharmaceutical CROs offer adaptable arrangements, making it simpler for organizations to grow their innovative work exercises without framework imperatives.

Why Choose Clinfinite Solutions?

Clinfinite Solutions stands apart as a head Pharmaceutical CRO, consolidating development, unwavering quality, and greatness. Our obligation to quality and client fulfillment has made us a confided-in accomplice for Pharmaceutical organizations around the world.

Demonstrated History

With long periods of involvement and various effective tasks, we have laid down a good foundation for ourselves as industry pioneers.

Client-Driven Approach

We focus on our client's objectives, keeping up with straightforward correspondence and conveying results that surpass assumptions.

Consistent Development

Clinfinite Solutions stays in front of industry patterns by embracing creative practices and coordinating cutting-edge innovations into our cycles.

Moral Norms

We stick to the most noteworthy moral principles, guaranteeing the respectability of clinical preliminaries and the government assistance of members.

Emerging Trends in Pharmaceutical CROs

As the Pharmaceutical business advances, CROs should adjust to recent fads and difficulties. Clinfinite Solutions is at the very front of these headways, embracing:

Decentralized Clinical Preliminaries (DCTs): Improving patient availability and commitment by leading preliminaries from a distance.

Artificial intelligence and Large Information Examination: Utilizing information experiences to further develop preliminary plan and execution.

Customized Medication: Supporting investigation into designated treatments and accurate medicines.

Manageability: Lessening the natural effect of clinical exploration through eco-accommodating practices.

Conclusion

The Pharmaceutical business' interest in creative treatments and smoothed out Pharmaceutical advancement has never been more prominent. Pharmaceutical CROs like Clinfinite Solutions assume a crucial part in conquering these difficulties, empowering organizations to put up groundbreaking medicines for sale to the public productively.

With an extensive set-up of administrations, a guarantee to greatness, and a client-driven approach, Clinfinite Solutions is your optimal accomplice for clinical innovative work. Whether you're a startup or a laid-out Pharmaceutical organization, we have the skills and assets to address your issues.

Pick Clinfinite Solutions as your confided-in Pharmaceutical CRO and venture out toward upsetting medical services. Together, we can have an effect on patients' lives around the world.