CC-90009: A Cereblon E3 Ligase Modulating Drug That Promotes Selective Degradation of GSPT1 for the Treatment of Acute Myeloid Leukemia.
Joshua D HansenMatthew CorreaMatt AlexanderMark NagyDehua HuangJohn SapienzaGang LuLaurie A LeBrunBrian E CathersWeihong ZhangYang TangMassimo AmmiranteRama K NarlaJoseph R PiccottiMichael PourdehnadAntonia Lopez-GironaPublished in: Journal of medicinal chemistry (2021)
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.
Keyphrases
- acute myeloid leukemia
- allogeneic hematopoietic stem cell transplantation
- signaling pathway
- end stage renal disease
- newly diagnosed
- emergency department
- acute lymphoblastic leukemia
- ejection fraction
- prognostic factors
- binding protein
- adverse drug
- diffuse large b cell lymphoma
- protein protein
- combination therapy
- data analysis