Advances in developing small molecule inhibitors of ubiquitin-specific protease 1
Ubiquitin-specific protease 1(USP1)is one of the deubiquitinating enzymes which has received increasing attention in cancer research.USP1 is overexpressed in many types of cancer cells,and has been found to control tumorigenesis and progression by regulating various proteins associated with tumors,such as SIK2,GSK-3β,and Bcl-2.Knockdown or pharmacological inhibition of USP1 can effectively suppress tumors and is also expected to address the issues of cisplatin and poly ADP-ribose polymerase(PARP)inhibitor resistance.This review describes the structure and function of USP1 and the relationship between USP1 targets and tumors and systematically summarizes the structure-activity relationships of small molecule USP1 inhibitors disclosed from 2013 to 2023.Finally,this review discusses the challenges and opportunities in developing small molecule USP1 inhibitors.
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