Small molecule-based immunomodulators for cancer therapy  

作　　者：Yinrong Wu Zichao Yang Kui Cheng Huichang Bi Jianjun Chen 

机构地区：[1]Guangdong Provincial Key Laboratory of New Drug Screening,NMPA Key Laboratory for Research and Evaluation of Drug Metabolism,School of Pharmaceutical Sciences,Southern Medical University,Guangzhou 510515,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第12期4287-4308,共22页药学学报（英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(No.82173668);Scientific Research Project of High-Level Talents(No.C1034335,China)in Southern Medical University of China;Thousand Youth Talents Program(No.C1080094,China)from the Organization Department of the CPC Central Committee,China.

摘　　要：Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immunotherapies are mostly antibody-based,thus possessing advantages in regard to pharmacodynamics(e.g.,specificity and efficacy).However,they have limitations in terms of pharmacokinetics including long half-lives,poor tissue/tumor penetration,and little/no oral bioavailability.In addition,therapeutic antibodies are immunogenic,thus may cause unwanted adverse effects.Therefore,researchers have shifted their efforts towards the development of small molecule-based cancer immunotherapy,as small molecules may overcome the above disadvantages associated with antibodies.Further,small molecule-based immunomodulators and therapeutic antibodies are complementary modalities for cancer treatment,and may be combined to elicit synergistic effects.Recent years have witnessed the rapid development of small molecule-based cancer immunotherapy.In this review,we describe the current progress in small molecule-based immunomodulators(inhibitors/agonists/degraders)for cancer therapy,including those targeting PD-1/PD-L1,chemokine receptors,stimulator of interferon genes(STING),Toll-like receptor(TLR),etc.The tumorigenesis mechanism of various targets and their respective modulators that have entered clinical trials are also summarized.

关 键 词：Cancer immunotherapy Small molecules IMMUNOMODULATORS INHIBITORS AGONISTS 

分 类 号：R979.1[医药卫生—药品]