Enitociclib, a selective CDK9 inhibitor: in vitro and in vivo preclinical studies in multiple myeloma
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 cycli...
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| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-02-01
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| Series: | Blood Neoplasia |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2950328024000505 |
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| Summary: | 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. |
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| ISSN: | 2950-3280 |