Immunotherapy has led to a paradigm shift in the treatment of cancer.Current cancer immu-notherapies 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 anti-bodies 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 immu-nomodulators 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.

Yinrong Wu;Zichao Yang;Kui Cheng;Huichang Bi;Jianjun Chen

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

药学学报（英文版）

[1]Yinrong Wu;Zichao Yang;Kui Cheng;Huichang Bi;Jianjun Chen-.Small molecule-based immunomodulators for cancer therapy)[J].药学学报（英文版）,2022(12):4287-4308

immunomodulators,notherapies,nomodulators,degraders

Small,cancer,Immunotherapy,has,led,paradigm,treatment,Current,are,mostly,antibody,thus,possessing,regard,pharmacodynamics,specificity,efficacy,However,they,have,limitations,terms,pharmacokinetics,including,long,half,lives,poor,tissue,penetration,little,oral,bioavailability,In,addition,therapeutic,immunogenic,may,cause,unwanted,adverse,effects,Therefore,researchers,shifted,their,efforts,towards,development,small,immunotherapy,molecules,overcome,above,disadvantages,associated,antibodies,Further,complementary,modalities,combined,elicit,synergistic,Recent,years,witnessed,rapid,this,review,describe,current,progress,inhibitors,agonists,those,targeting,L1,chemokine,receptors,stimulator,interferon,STING,Toll,like,TLR,etc,tumorigenesis,mechanism,various,targets,respective,that,entered,clinical,trials,also,summarized

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