Development of small molecule drugs targeting immune checkpoints  

作　　者：Luoyi Chen Xinchen Zhao Xiaowei Liu Yujie Ouyang Chuan Xu Ying Shi 

机构地区：[1]Department of Oncology,Sichuan Academy of Medical Sciences,Sichuan Provincial People’s Hospital,School of Medicine,University of Electronic Science and Technology of China,Chengdu 610054,China [2]Institute for Breast Health Medicine,State Key Laboratory of Biotherapy,West China Hospital,Sichuan University,Chengdu 610041,China [3]Acupuncture and Massage College,Chengdu University of Traditional Chinese Medicine,Chengdu 611137,China

出　　处：《Cancer Biology & Medicine》2024年第5期382-399,共18页癌症生物学与医学（英文版）

基　　金：supported by the National Natural Science Foundation of China(Grant Nos.82203539 and 92259102);Provincial Cooperation Project of Science and Technology Department of Sichuan Province(Grant No.2023YFSY0043);the National Key Research and Development Program of China(Grant No.2023YFC3402100).

摘　　要：Immune checkpoint inhibitors(ICIs)are used to relieve and refuel anti-tumor immunity by blocking the interaction,transcription,and translation of co-inhibitory immune checkpoints or degrading co-inhibitory immune checkpoints.Thousands of small molecule drugs or biological materials,especially antibody-based ICIs,are actively being studied and antibodies are currently widely used.Limitations,such as anti-tumor efficacy,poor membrane permeability,and unneglected tolerance issues of antibody-based ICIs,remain evident but are thought to be overcome by small molecule drugs.Recent structural studies have broadened the scope of candidate immune checkpoint molecules,as well as innovative chemical inhibitors.By way of comparison,small molecule drug-based ICIs represent superior oral bioavailability and favorable pharmacokinetic features.Several ongoing clinical trials are exploring the synergetic effect of ICIs and other therapeutic strategies based on multiple ICI functions,including immune regulation,anti-angiogenesis,and cell cycle regulation.In this review we summarized the current progression of small molecule ICIs and the mechanism underlying immune checkpoint proteins,which will lay the foundation for further exploration.

关 键 词：Immune checkpoints small molecule drugs programmed death protein 1 CD47 signal-regulatory proteinα 

分 类 号：R979.1[医药卫生—药品]