Mezigdomide (BMS-986348)

Mechanism of action

From the NCI Drug Dictionary: A modulator of the E3 ubiquitin ligase complex containing cereblon (CRL4-CRBN E3 ubiquitin ligase), with potential immunomodulating and antineoplastic activities. Upon administration, mezigdomide specifically binds to cereblon (CRBN), thereby affecting the ubiquitin E3 ligase activity, and targeting certain substrate proteins for ubiquitination. This induces proteasome-mediated degradation of certain transcription factors, some of which are transcriptional repressors in T cells. This leads to modulation of the immune system, including activation of T lymphocytes, and downregulation of the activity of other proteins, some of which play key roles in the proliferation of certain cancer cell types.

• IUPHAR/BPS

Preliminary data

1. CC-92480-MM-001: Richardson PG, Trudel S, Popat R, Mateos MV, Vangsted AJ, Ramasamy K, Martinez-Lopez J, Quach H, Orlowski RZ, Arnao M, Lonial S, Karanes C, Pawlyn C, Kim K, Oriol A, Berdeja JG, Rodríguez Otero P, Casas-Avilés I, Spirli A, Poon J, Li S, Gong J, Wong L, Lamba M, Pierce DW, Amatangelo M, Peluso T, Maciag P, Katz J, Pourdehnad M, Bahlis NJ; CC-92480-MM-001 Study Investigators. Mezigdomide plus Dexamethasone in Relapsed and Refractory Multiple Myeloma. N Engl J Med. 2023 Sep 14;389(11):1009-1022. Epub 2023 Aug 30. link to original article PubMed NCT03374085

Also known as

• Code names: BMS-986348, CC-92480