数量结构-活动关系
吲哚
对接(动物)
分子动力学
化学
分子模型
脚手架
计算生物学
立体化学
组合化学
计算化学
计算机科学
生物
医学
护理部
数据库
作者
J. Tong,Peng Gao,Xuechun Xiao,Yuan Liu,Hai‐Yin Xu
标识
DOI:10.1002/slct.202302813
摘要
Abstract In recent years, blocking the interaction of programmed cell death receptor‐1 (PD‐1) and programmed cell death ligand‐1 (PD‐L1) has been recognized as one of the promising cancer therapies. Due to the many limitations of monoclonal antibodies, the development of small molecule inhibitors targeting PD‐1/PD‐L1 is imminent. This study aims to systematically investigate the interaction mechanisms of novel PD‐1/PD‐L1 inhibitors containing indoline backbone structures using 3D/2D‐QSAR modeling, molecular docking, molecular dynamics (MD) simulation, and ADMET prediction. The performance and predictive ability of the constructed QSAR models were evaluated by internal and external validation techniques. Topomer CoMFA and HQSAR models showed good reliability and predictive capability. By searching for R‐groups in the Topomer search module and combining the existing molecules with high activity contribution values, 24 new compounds with theoretically high activity were obtained, which showed desirable docking scores, appropriate ADMET properties, and good stability. This work not only provides a reliable QSAR model as a valuable screening tool for the development of future drugs targeting PD‐1/PD‐L1, but also makes the newly designed inhibitors expected to be potential PD‐1/PD‐L1 inhibitors that can be used for further synthesis and characterization to obtain novel anti‐cancer drugs targeting PD‐1/PD‐L1.
科研通智能强力驱动
Strongly Powered by AbleSci AI