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7133997 
Journal Article 
A novel cereblon modulator for targeted protein degradation 
Kim, SA; Go, A; Jo, SH; Park, SJ; Jeon, YU; Kim, JE; Lee, HK; Park, CH; Lee, CO; Park, SG; Kim, P; Park, BC; Cho, SY; Kim, S; Ha, JD; Kim, JH; Hwang, JY; , 
2019 
Yes 
European Journal of Medicinal Chemistry
ISSN: 0223-5234
EISSN: 1768-3254 
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER 
ISSY-LES-MOULINEAUX 
65-74 
English 
30684871 
WOS:000461402400006 
Immunomodulatory drugs (IMiDs) exert anti-myeloma activity by binding to the protein cereblon (CRBN) and subsequently degrading IKZF1/3. Recently, their ability to recruit E3 ubiquitin ligase has been used in the proteolysis targeting chimera (PROTAC) technology. Herein, we design and synthesize a novel IMiD analog TD-106 that induces the degradation of IKZF1/3 and inhibits the proliferation of multiple myeloma cells in vitro as well as in vivo. Moreover, we demonstrate that TD-428, which comprises TD-106 linked to a BET inhibitor, JQ1 efficiently induce BET protein degradation in the prostate cancer cell line 22Rv1. Consequently, cell proliferation is inhibited due to suppressed C-MYC transcription. These results, therefore, firmly suggest that the newly synthesized IMiD analog, TD-106, is a novel CRBN modulator that can be used for targeted protein degradation.