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molecules of the month

CC-90009

CRBN-based GSPT1 molecular glue degrader

intravenous agent in Ph. I for AML + MDS

from phenotypic screen of CRBN mod library

J. Med. Chem., Feb. 16, 2021

Celgene/Bristol Myers Squibb, San Diego, CA

CC-90009
1 min read

1. The Bristol Myers Squibb (BMS)/Celgene GSPT1 degrader (CC-90009) is a CRBN-based molecular glue (CELMoD). It is a clinical candidate in Ph. I for AML and MDS, and in contrast to CC-92480 highlighted last March, spares the primary targets of prior imide drugs (IKZF1/3) and instead selectively degrades GSPT1. The starting point was identified through a phenotypic screen against a panel of AML cell lines using their cereblon (CRBN) modulator library and the nontumor human epithelial cell line (THLE-2) as a counterscreen. Clinically, at a dose of 2.4 mg, 90% GSPT1 reduction was observed, representing an important proof-of-concept for expanding the scope of molecular glue-type degraders.


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