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

{"title":"Enitociclib, a selective CDK9 inhibitor: in vitro and in vivo preclinical studies in multiple myeloma","authors":"Son Tran ,&nbsp;Patrick Sipila ,&nbsp;Melanie M. Frigault ,&nbsp;Beatrix Stelte-Ludwig ,&nbsp;Amy J. Johnson ,&nbsp;Joseph Birkett ,&nbsp;Raquel Izumi ,&nbsp;Ahmed Hamdy ,&nbsp;Ranjan Maity ,&nbsp;Nizar J. Bahlis ,&nbsp;Paola Neri ,&nbsp;Aru Narendran","doi":"10.1016/j.bneo.2024.100050","DOIUrl":null,"url":null,"abstract":"<div><h3>Abstract</h3><div>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.</div></div>","PeriodicalId":100189,"journal":{"name":"Blood Neoplasia","volume":"2 1","pages":"Article 100050"},"PeriodicalIF":0.0000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Blood Neoplasia","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S2950328024000505","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}