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

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

  • J Med Chem. 2021 Feb 25;64(4):1835-1843. doi: 10.1021/acs.jmedchem.0c01489.
Joshua D Hansen 1,  Matthew Correa 1,  Matt Alexander 1,  Mark Nagy 1,  Dehua Huang 1,  John Sapienza 1,  Gang Lu 1,  Laurie A LeBrun 1,  Brian E Cathers 1,  Weihong Zhang 2,  Yang Tang 1,  Massimo Ammirante 1,  Rama K Narla 1,  Joseph R Piccotti 1,  Michael Pourdehnad 3,  Antonia Lopez-Girona 1
Affiliations

Affiliations

  • 1 Bristol Myers Squibb, 10300 Campus Point Drive, Suite 100, San Diego, California 92121, United States.
  • 2 Bristol Myers Squibb, 556 Morris Avenue, Summit, New Jersey 07901, United States.
  • 3 Bristol Myers Squibb, 1500 Owens Street, Suite 600, San Francisco, California 94158, United States.
PMID: 33591756 DOI: 10.1021/acs.jmedchem.0c01489
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.

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