2024年首创性小分子药物研究实例浅析  

First-in-class small molecule drugs in 2024

作　　者：王磊[1,2] 尤启冬 WANG Lei;YOU Qi-dong(Jiangsu Key Laboratory of Drug Design and Optimization,China Pharmaceutical University,Nanjing 210009,China;Department of Medicinal Chemistry,School of Pharmacy,China Pharmaceutical University,Nanjing 210009,China)

机构地区：[1]中国药科大学,江苏省创新药物设计与成药性优化重点实验室,江苏南京210009 [2]中国药科大学药学院药物化学系,江苏南京210009

出　　处：《药学学报》2025年第4期843-852,共10页Acta Pharmaceutica Sinica

摘　　要：2024年新药研发持续发力,首创性药物的上市数量再创新高。美国FDA药物评价和研究中心在过去一年里共计批准了50款新药,其中包括30款小分子药物及20款大分子药物。新药总数相比2023年的55款略有下降,但首创性药物占比明显增加。本年度获批24款首创性药物(48%),涵盖13款小分子首创性药物和11款大分子首创药物,多数集中于肿瘤、内分泌及代谢疾病领域。其中,多个首创性小分子药物具有突破性的临床价值,例如首个M1/M4毒蕈碱受体激动剂/外周毒蕈碱受体拮抗剂呫诺美林/曲司氯铵,首个甲状腺素受体β亚型激动剂瑞司美替罗,首个用于高血压治疗的内皮素受体A及内皮素受体B受体双重拮抗剂阿普昔腾坦等。首创性药物具有巨大的临床价值、学术价值及商业价值,受到来自患者、研究人员及企业的广泛关注。本文通过药物化学角度浅析本年度3个代表性首创性小分子药物的研发背景、研发过程和治疗应用,以期为首创性药物的研发提供更多的研究方向与方法。In 2024,drug discovery continues to develop on the basis of the achievement before.The number of approved first-in-class(FIC)drugs reach a higher level.The Center for Drug Evaluation and Research of U.S.Food and Drug Administration has totally approved 50 novel drugs,including 30 small molecule drugs and 20macromolecule drugs.Comparing to the number of approved drugs in 2023,the total in 2024 falls slightly.But the proportion of FIC drugs increase obviously.There are 24 FIC drugs(48%)approved in 2024,which include 13 FIC small molecule drugs and 11 FIC macromolecule drugs and whose indications mainly focus on tumor,and endocrine and metabolic disease.Among 24 FIC drugs,many drugs have breakthrough clinical value,such as the first combination of muscarinic acetylcholine receptor M1/M4 agonist and peripheral muscarinic acetylcholine receptor antagonist,xanomeline and trospium chloride,the first thyroid hormone receptor beta agonist,resmetirom,the first dual antagonist of endothelin receptor type A and B to treat hypertension,aprocitentan.The huge value of FIC drugs in clinical therapy,academic research and commerce,is attracting wide attention from the patients,researchers and enterprises.This review will analyze the research background,development process and therapeutic application of three first-in-class small molecule drugs in this year from a medicinal chemistry perspective,expecting to provide more research directions and methods for the development and research of FIC drugs.

关 键 词：首创性药物 新药研发 小分子药物 

分 类 号：R914[医药卫生—药物化学]