化学
赫拉
效力
IC50型
体内
免疫疗法
药理学
抑制性突触后电位
吲哚胺2,3-双加氧酶
癌症免疫疗法
肺癌
立体化学
体外
癌症
组合化学
生物化学
肿瘤科
内科学
氨基酸
生物技术
色氨酸
生物
医学
作者
Qianming Du,Xi Feng,Yinuo Wang,Xi Xu,Yan Zhang,Xinliang Qu,Zhiyu Li,Jinlei Bian
标识
DOI:10.1016/j.ejmech.2019.111629
摘要
Targeting indoleamine 2,3-dioxygenase 1 (IDO1) has been identified as an attractive approach for the development of cancer immunotherapy. In this study, a series of phosphonamidate ester containing compounds were designed, synthesized and evaluated for their inhibitory activities against IDO1. Among them, compounds 16, 17, and 26 with good IDO1 inhibitory (HeLa IDO1 IC50 = 10-21 nM, hIDO1 IC50 = 78-121 nM) activities were selected for further investigation and showed good physicochemical properties. Furthermore, based on comparable PK profile and excellent IDO2/TDO inhibitory potency, representative compound 16 was selected for further bio-evaluation and characterized with good efficacy in suppressing lung metastasis (77% inhibition rate) of Lewis cells in vivo. Thus, compound 16 could be a potential and efficacious agent for further evaluation.
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