Enitociclib, a selective CDK9 inhibitor: in vitro and in vivo preclinical studies in multiple myeloma.

Authors

Son Tran, Patrick Sipila, Melanie M Frigault, Beatrix Stelte-Ludwig, Amy J Johnson, Joseph Birkett, Raquel Izumi, Ahmed Hamdy, Ranjan Maity, Nizar J Bahlis, Paola Neri, Aru Narendran

Published in

Blood neoplasia. Volume 2. Issue 1. Pages 100050. Epub Oct 24, 2024.

Abstract

Multiple myeloma (MM) is a cancer of plasma cells that remains incurable despite advances in treatment options. In this study, a library of 216 clinically feasible small-molecule inhibitors was screened to identify agents that selectively inhibit MM cell proliferation. Enitociclib, a cyclin-dependent kinase 9-specific small-molecule inhibitor, was found to be highly effective in decreasing cell viability and inducing apoptosis in 4 MM cell lines. Enitociclib inhibited the phosphorylation of the carboxy-terminal domain (CTD) of RNA polymerase II at Ser2/Ser5 and repressed the protein expression of oncogenes c-Myc, myeloid cell leukemia-1 (Mcl-1), and proliferating cell nuclear antigen (PCNA) in MM cells. Additionally, enitociclib demonstrated synergistic effects with several anti-MM agents, including bortezomib, lenalidomide, pomalidomide, and venetoclax. These results suggest that enitociclib may represent a promising therapeutic option for the treatment of MM, either as a single agent or in combination with other anti-MM agents.

PMID:
40546728
Bibliographic data and abstract were imported from PubMed on 24 Jun 2025.

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