酪氨酸激酶2
变构调节
化学
药物发现
贾纳斯激酶
酪氨酸激酶
哒嗪
酪氨酸激酶抑制剂
激酶
计算生物学
生物化学
药理学
酶
立体化学
受体
生物
血小板源性生长因子受体
遗传学
癌症
生长因子
作者
Yu Ming Chang,Shilin Xu,Ke Ding
标识
DOI:10.1021/acs.jmedchem.9b01612
摘要
TYK2 is an emerging drug target for various human autoimmune diseases. However, discovery of selective TYK2 inhibitor over other JAK family members (i.e., JAK1, 2, 3) by targeting the catalytically active site (Janus Homologue 1 (JH1) domain) is challenging. This Viewpoint discusses the discovery of a series of N-methyl pyridazine-3-carboxamides as novel selective pseudokinase (JH2) domain binders of TYK2. A systematic structure-based optimization yielded a highly potent and selective allosteric TYK2 inhibitor candidate that is currently in phase III clinical trial for psoriasis.
科研通智能强力驱动
Strongly Powered by AbleSci AI