Structure-activity relationship study of PROTACs against hematopoietic prostaglandin D₂ synthase.

ABSTRACT: Degradation of hematopoietic prostaglandin D₂ synthase (H-PGDS) by proteolysis-targeting chimeras (PROTACs) is expected to be important in the treatment of allergic diseases and Duchenne's muscular dystrophy. We recently reported that PROTAC(H-PGDS)-7 (PROTAC1), which is composed of H-PGDS inhibitor (TFC-007) and cereblon (CRBN) E3 ligase ligand (pomalidomide), showed potent H-PGDS degradation activity. Here, we investigated the structure-activity relationships of PROTAC1, focusing on the C4- or C5-conjugation of pomalidomide, in addition, the H-PGDS ligand exchanging from TFC-007 with the biaryl ether to TAS-205 with the pyrrole. Three new PROTACs were evaluated for H-PGDS affinity, H-PGDS degrading activity, and inhibition of prostaglandin D₂ pr

SUBMITTER: Murakami Y 

PROVIDER: S-EPMC9749925 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature