变构调节
原肌球蛋白受体激酶A
化学
虚拟筛选
低亲和力神经生长因子受体
药理学
结构-活动关系
变构调节剂
药物发现
受体
生物化学
神经生长因子
生物
体外
作者
Jing Guo,Shuang Xiang,Jie Wang,Yang Zhou,Zuqin Wang,Zhang Zhang,Ke Ding,Xiaoyun Lu
标识
DOI:10.1016/j.ejmech.2021.114022
摘要
Tropomyosin receptor kinases A (TrkA) is a potential therapeutic target for the treatment of numerous tumor types and chronic pain. However, most of the reported TrkA inhibitors are ATP competitive pan-Trks inhibitors that lack subtype selectivity. A selective TrkA inhibitor may provide valuable therapeutic benefits. Here, we described the discovery of novel TrkA allosteric inhibitors by structure-based virtual screening. A promising hit (D5261, TrkA cell IC50 = 3.32 μM) was selected for further studies. The binding free energy between TrkA and D5261 was calculated. In addition, the preliminary structure-activity relationship (SAR) studies with D5261 were investigated. The results suggest that D5261 can be used as a starting point for development of TrkA allosteric inhibitors.
科研通智能强力驱动
Strongly Powered by AbleSci AI