Akshay D Takwale, Eun Yeong Kim, Yerin Jang, Dong Ho Lee, Seulgi Kim, Yuri Choi, Jin Hwan Kim, Da Yeon Lee, Yeongrin Kim, So Myoung Lee, Heung Kyoung Lee, Hye Jin Nam, Joo-Youn Lee, Jin Hwa Cho, Jeong Hee Moon, Ga Seul Lee, Jeong-Hoon Kim, Pilho Kim, Chi Hoon Park, Jong Yeon Hwang
Molecular glue degraders, such as lenalidomide and pomalidomide, bind to cereblon (CRBN) E3 ligase and subsequently recruit neosubstrate proteins, Ikaros (IKZF1) and Aiolos (IKZF3), for the ubiquitination-proteasomal degradation process. In this study, we explored structure-activity relationship analysis for novel GSPT1 degraders utilizing a benzotriazinone scaffold previously discovered as a novel CRBN binder. In particular, we focused on the position of the ureido group on the benzotriazinone scaffold, substituent effect on the phenylureido group, and methyl substitution on the benzylic position of benzotriazinone...
October 2022: Bioorganic Chemistry