scholarly journals Clinical Trial Risk in Hepatitis C: Endpoint Selection and Drug Action

2016 ◽  
Vol 2016 ◽  
pp. 1-7
Author(s):  
Nicole A. Tillie ◽  
Jayson L. Parker ◽  
Jordan J. Feld
Keyword(s):  
Clinical Trial ◽  
Hepatitis C ◽  
Small Molecule ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Pass Rate ◽  
Success Rates ◽  
Small Molecule Drugs ◽  
Drug Compounds ◽  
Viral Inhibitor

Background and Aims.This study analyzed the risk of clinical trial failure of new drugs for hepatitis C between January 1998 and January 2015.Methods.Hepatitis C drug development trials that were in phases I–III of clinical trial testing were obtained from the publicly accessible clinical trial repository and other publicly available databases. Drug compounds were excluded from the study if they began their phase I testing before 1998, if they were not industry sponsored, or if they treated secondary complications of hepatitis C. Clinical trial success rates were analyzed in comparison to industry expectations. Further analysis was conducted on the molecule classifications, the mechanisms of action, and the trial endpoints.Results.One hundred and twenty-three unique drug compounds were found to fulfill the inclusion criteria, eight of which had FDA approval. The overall cumulative pass rate for hepatitis C drugs was 20%, which is double the industry expectation rate. Viral inhibitor small molecule drugs significantly reduced the risk of drug failure during clinical trials compared to other mechanisms of action.Conclusion.On average, one in every five drugs that began clinical testing will be approved for market. Viral inhibitor small molecule drugs are the most promising and hold the least risk.

scholarly journals The Benefits From Giving Makers Of Conventional ‘Small Molecule’ Drugs Longer Exclusivity Over Clinical Trial Data

2011 ◽  
Vol 30 (1) ◽  
pp. 84-90 ◽  
Author(s):  
Dana P. Goldman ◽  
Darius N. Lakdawalla ◽  
Jesse D. Malkin ◽  
John Romley ◽  
Tomas Philipson
Keyword(s):  
Clinical Trial ◽  
Small Molecule ◽  
Clinical Trial Data ◽  
Trial Data ◽  
Small Molecule Drugs

Antioxidant and Antibacterial Activity of Sulfonamides Derived from Carvacrol: A Structure-Activity Relationship Study

2020 ◽  
Vol 20 (3) ◽  
pp. 173-181 ◽  
Author(s):  
Aldo S. de Oliveira ◽  
Luiz F. S. de Souza ◽  
Ricardo J. Nunes ◽  
Susana Johann ◽  
David L. Palomino-Salcedo ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Biological Activity ◽  
Molecular Docking ◽  
Small Molecule ◽  
Bacterial Resistance ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Structure Activity ◽  
Relationship Study ◽  
Antibacterial Potential

Background: Bacterial resistance to antibiotics is a growing problem in all countries and has been discussed worldwide. In this sense, the development of new drugs with antibiotic properties is highly desirable in the context of medicinal chemistry. Methodology: In this paper we investigate the antioxidant and antibacterial potential of sulfonamides derived from carvacrol, a small molecule with drug-like properties. Most sulfonamides had antioxidant and antibacterial potential, especially compound S-6, derived from beta-naphthylamine. Result: To understand the possible mechanisms of action involved in biological activity, the experimental results were compared with molecular docking data. Conclusion: This research allows appropriate discussion on the identified structure activity relationships.

scholarly journals Mechanisms of Action for Small Molecules Revealed by Structural Biology in Drug Discovery

2020 ◽  
Vol 21 (15) ◽  
pp. 5262 ◽  
Author(s):  
Qingxin Li ◽  
CongBao Kang
Keyword(s):  
Drug Discovery ◽  
Small Molecules ◽  
Structural Biology ◽  
Small Molecule ◽  
Molecular Interactions ◽  
Mechanisms Of Action ◽  
Rational Drug Design ◽  
Binding Modes ◽  
Small Molecule Drugs ◽  
Rational Drug

Small-molecule drugs are organic compounds affecting molecular pathways by targeting important proteins. These compounds have a low molecular weight, making them penetrate cells easily. Small-molecule drugs can be developed from leads derived from rational drug design or isolated from natural resources. A target-based drug discovery project usually includes target identification, target validation, hit identification, hit to lead and lead optimization. Understanding molecular interactions between small molecules and their targets is critical in drug discovery. Although many biophysical and biochemical methods are able to elucidate molecular interactions of small molecules with their targets, structural biology is the most powerful tool to determine the mechanisms of action for both targets and the developed compounds. Herein, we reviewed the application of structural biology to investigate binding modes of orthosteric and allosteric inhibitors. It is exemplified that structural biology provides a clear view of the binding modes of protease inhibitors and phosphatase inhibitors. We also demonstrate that structural biology provides insights into the function of a target and identifies a druggable site for rational drug design.

scholarly journals Emerging small-molecule treatments for multiple sclerosis: focus on B cells

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 245 ◽  
Author(s):  
Aaron Gregson ◽  
Kaitlyn Thompson ◽  
Stella E Tsirka ◽  
David L Selwood
Keyword(s):  
Multiple Sclerosis ◽  
B Cells ◽  
B Cell ◽  
Small Molecule ◽  
Cell Biology ◽  
New Drugs ◽  
Risk Genes ◽  
Small Molecule Drugs ◽  
Patent Term ◽  
B Cell Subsets

Multiple sclerosis (MS) is a major cause of disability in young adults. Following an unknown trigger (or triggers), the immune system attacks the myelin sheath surrounding axons, leading to progressive nerve cell death. Antibodies and small-molecule drugs directed against B cells have demonstrated good efficacy in slowing progression of the disease. This review focusses on small-molecule drugs that can affect B-cell biology and may have utility in disease management. The risk genes for MS are examined from the drug target perspective. Existing small-molecule therapies for MS with B-cell actions together with new drugs in development are described. The potential for experimental molecules with B-cell effects is also considered. Small molecules can have diverse actions on B cells and be cytotoxic, anti-inflammatory and anti-viral. The current B cell–directed therapies often kill B-cell subsets, which can be effective but lead to side effects and toxicity. A deeper understanding of B-cell biology and the effect on MS disease should lead to new drugs with better selectivity, efficacy, and an improved safety profile. Small-molecule drugs, once the patent term has expired, provide a uniquely sustainable form of healthcare.

scholarly journals The Success Rate of New Drug Development in Clinical Trials: Crohn’s Disease

2010 ◽  
Vol 13 (2) ◽  
pp. 191 ◽  
Author(s):  
Jayson Lee Parker ◽  
Jillian Clare Kohler
Keyword(s):  
Clinical Trial ◽  
Crohn’S Disease ◽  
Crohn's Disease ◽  
Drug Development ◽  
Success Rate ◽  
Small Molecule ◽  
New Drugs ◽  
Press Releases ◽  
New Drug ◽  
Trial Testing

Purpose. To determine the risk of drug failure during clinical trial testing in Crohn’s disease and determine what steps can be taken to improve outcomes. This is the first study to quantify such risk for a single disease. Methods. Moderate to severe Crohn’s disease was investigated by reviewing press releases from 1998 to June 2008. Clinical trial failure causes were classified as commercial or clinical and compared with industry expectations. The risk of failure was also reviewed based on whether the compound was a small molecule drug or a biologic. Lastly, the role of the sponsor was examined, in determining whether the size of the firm involved in a drug program was predictive of the outcome of the study. Results. More than a120 press releases were reviewed yielding 37 drugs that met our search criteria. The cumulative success rate for drug development in Crohn’s disease is 19%, from start to finish of clinical trial testing. New drug approvals are dominated by protein based therapeutics in this indication. Commercial and clinical failures both contributed substantially to the failure rates of new drugs. Phase I clinical testing appeared to offer little risk mitigation with pass rates at 95%. Conclusion. Funding intended to advance Crohn’s disease must take into account the disease specific historical failure rate of drug development in forecasting any reasonable expectation of producing new therapies. As it currently stands, one in five drugs will be successfully approved that enter clinical trial testing in this indication. To manage this risk continued development of biologics over small molecule drugs may be warranted in this disease.

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