Department of Quantitative Biology , Arcus Biosciences, Inc. , 3928 Point Eden Way , Hayward , California 94545 , United States.
School of Biology, Biomedical Sciences Research Complex , University of St Andrews , St Andrews , Fife KY16 9ST , United Kingdom.
Biochemistry. 2019 Aug 6;58(31):3331-3334. doi: 10.1021/acs.biochem.9b00448. Epub 2019 Jul 23.
We recently reported the initiation of a Phase I clinical trial with AB680, a potent human CD73 inhibitor, being developed for the treatment of solid tumors (NCT03677973). We undertook a detailed kinetic analysis of the interaction between human CD73 and AB680 to determine the mode of inhibition. We found AB680 to be a reversible, slow-onset competitive inhibitor of human CD73 with a of 5 pM. Clinical candidates of this potency are uncommon and deserve special consideration during lead optimization.
我们最近报告了一项 I 期临床试验的启动，该试验使用 AB680（一种强效的人 CD73 抑制剂）治疗实体瘤（NCT03677973）。我们对人 CD73 与 AB680 之间的相互作用进行了详细的动力学分析，以确定抑制模式。我们发现 AB680 是人 CD73 的可逆、缓慢起始的竞争性抑制剂， 为 5 pM。这种效力的临床候选药物并不常见，在先导化合物优化过程中值得特别考虑。
