%0 Journal Article
%T Small molecules as antagonists of co-inhibitory pathways for cancer immunotherapy: a patent review (2018-2019).
%A Geng Q
%A Rohondia SO
%A Khan HJ
%A Jiao P
%A Dou QP
%J Expert Opin Ther Pat
%V 30
%N 9
%D Sep 2020
%M 32715813
%F 6.714
%R 10.1080/13543776.2020.1801640
%X <B>BACKGROUND: </B>Therapeutic antibodies blocking co-inhibitory pathways do not attack tumor cells directly, but instead bind to their targeted proteins and mobilize the immune system to eradicate tumors. However, only a small fraction of patients with certain cancer types can benefit from the antibodies. Additionally, antibodies have shown serious immune-related adverse events in certain patients. Small-molecule antagonists may be a complementary and potentially synergistic approach to antibodies for patients with various cancers.<BR><B>UNASSIGNED: </B>The authors review the small molecules as antagonists of co-inhibitory pathway proteins, summarize their preliminary SARs, discuss biochemistry assays used in patents for the development of small molecules as novel antagonists.<BR><B>UNASSIGNED: </B>The disclosed pharmacophores of small molecules as co-inhibitory pathway antagonists are represented by biphenyl derivatives, biaryl derivatives, teraryl derivatives, quateraryl derivatives, and oxadiazole/thiadiazole derivatives. However, these antagonists are still inferior to therapeutic antibodies in their inhibitory activities due to relatively flat of human co-inhibitory pathways proteins. Allosteric modulators may be an alternative approach. The more safety and efficacy evaluation trials of small-molecule antagonists targeting co-inhibitory pathways should be performed to demonstrate the proof-of-principle that small-molecule antagonists can result in sustained safety and antitumor response in the near future.