Pharmaceutical Candidate Optimization, Biocon Bristol-Myers Squibb R&D Centre, Syngene International Limited, Bangalore 560099, India.
Department of Pharmacy, Birla Institute of Technology and Science (BITS) Pilani, Pilani Campus, Rajasthan 333031, India.
J Med Chem. 2021 Mar 11;64(5):2339-2381. doi: 10.1021/acs.jmedchem.0c01786. Epub 2021 Feb 22.
In the present work, we report compilation and analysis of 245 drugs, including small and macromolecules approved by the U.S. FDA from 2015 until June 2020. Nearly 29% of the drugs were approved for the treatment of various types of cancers. Other major therapeutic areas of focus were infectious diseases (14%); neurological conditions (12%); and genetic, metabolic, and cardiovascular disorders (7-8% each). Itemization of the approved drugs according to the year of approval, sponsor, target, chemical class, major drug-metabolizing enzyme(s), route of administration/elimination, and drug-drug interaction liability (perpetrator or/and victim) is presented and discussed. An effort has been made to analyze the pharmacophores to identify the structural (e.g., aromatic, heterocycle, and aliphatic), elemental (e.g., boron, sulfur, fluorine, phosphorus, and deuterium), and functional group (e.g., nitro drugs) diversity among the approved drugs. Further, descriptor-based chemical space analysis of FDA approved drugs and several strategies utilized for optimizing metabolism leading to their discoveries have been emphasized. Finally, an analysis of drug-likeness for the approved drugs is presented.
在本工作中,我们报告了从 2015 年到 2020 年 6 月,美国食品和药物管理局(FDA)批准的 245 种药物(包括小分子和大分子)的编译和分析。近 29%的药物被批准用于治疗各种类型的癌症。其他主要治疗领域包括传染病(14%);神经系统疾病(12%);以及遗传、代谢和心血管疾病(各占 7-8%)。根据批准年份、赞助商、靶点、化学类别、主要药物代谢酶、给药途径/消除途径以及药物相互作用责任(肇事者或/和受害者)对批准药物进行了分类,并进行了讨论。我们努力分析药效团,以确定批准药物中的结构(例如芳香族、杂环和脂肪族)、元素(例如硼、硫、氟、磷和氘)和功能基团(例如硝基药物)多样性。此外,还强调了基于描述符的 FDA 批准药物的化学空间分析以及用于优化代谢以发现这些药物的几种策略。最后,还对批准药物的类药性进行了分析。