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ID: ALA4706692

Journal: J Med Chem

Title: CC-90009: A Cereblon E3 Ligase Modulating Drug That Promotes Selective Degradation of GSPT1 for the Treatment of Acute Myeloid Leukemia.

Authors: Hansen JD,Correa M,Alexander M,Nagy M,Huang D,Sapienza J,Lu G,LeBrun LA,Cathers BE,Zhang W,Tang Y,Ammirante M,Narla RK,Piccotti JR,Pourdehnad M,Lopez-Girona A

Abstract: Acute myeloid leukemia (AML) is marked by significant unmet clinical need due to both poor survival and high relapse rates where long-term disease control for most patients with relapsed or refractory AML remain dismal. Inspired to bring novel therapeutic options to these patients, we envisioned protein degradation as a potential therapeutic approach for the treatment of AML. Following this course, we discovered and pioneered a novel mechanism of action which culminated in the discovery of CC-90009. CC-90009 represents a novel protein degrader and the first cereblon E3 ligase modulating drug to enter clinical development that specifically targets GSPT1 (G1 to S phase transition 1) for proteasomal degradation. This manuscript briefly summarizes the mechanism of action, scientific rationale, medicinal chemistry, pharmacokinetic properties, and efficacy data for CC-90009, which is currently in phase 1 clinical development.

CiteXplore: 33591756

DOI: 10.1021/acs.jmedchem.0c01489