化学
小分子
共价键
蛋白质-蛋白质相互作用
单克隆抗体
配体(生物化学)
程序性细胞死亡
PD-L1
共价结合
计算生物学
生物化学
组合化学
细胞生物学
抗体
酶
受体
细胞凋亡
免疫系统
生物
免疫疗法
免疫学
有机化学
作者
Binbin Cheng,Yao Xiao,Mingming Xue,Hao Cao,Jianjun Chen
标识
DOI:10.1021/acs.jmedchem.0c01362
摘要
Therapeutic interference of the programmed cell death protein 1(PD-1)/immunosuppressive programmed cell death ligand 1 (PD-L1) signaling pathway by monoclonal antibodies has achieved spectacular success for treating various tumors. However, the development of small molecule inhibitors of PD-1/PD-L1 has lagged far behind due to the challenge of targeting the highly hydrophobic and relatively flat binding interface, despite the benefits small molecule can bring over therapeutic antibodies. This technical challenge provokes the adoption of different strategies in searching for small, medium-sized, and large molecule modulators (e.g., degraders, downregulators, and covalent inhibitors) of the PD-1/PD-L1 protein–protein interaction. In this review article, we discuss latest advances in the development of PD-L1 modulators, with a focus on degraders, downregulators, and covalent inhibitors.
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