15357163mct130849-sup-tab_2_excel.xlsx (54.73 kB)
Supplementary Table 2 from A Novel CDK9 Inhibitor Shows Potent Antitumor Efficacy in Preclinical Hematologic Tumor Models
datasetposted on 2023-04-03, 14:03 authored by Tinggui Yin, Maria J. Lallena, Emiko L. Kreklau, Kevin R. Fales, Santiago Carballares, Raquel Torrres, Graham N. Wishart, Rose T. Ajamie, Damien M. Cronier, Phillip W. Iversen, Timothy I. Meier, Robert T. Foreman, Douglas Zeckner, Sean E. Sissons, Bart W. Halstead, Aimee B. Lin, Gregory P. Donoho, Yuewei Qian, Shuyu Li, Song Wu, Amit Aggarwal, Xiang S. Ye, James J. Starling, Richard B. Gaynor, Alfonso de Dios, Jian Du
XLSX - 54K, Table S2. 261 probsets gene signature in sens and res cell lines in Excel format.
ARTICLE ABSTRACTDNA-dependent RNA polymerase II (RNAP II) largest subunit RPB1 C-terminal domain (CTD) kinases, including CDK9, are serine/threonine kinases known to regulate transcriptional initiation and elongation by phosphorylating Ser 2, 5, and 7 residues on CTD. Given the reported dysregulation of these kinases in some cancers, we asked whether inhibiting CDK9 may induce stress response and preferentially kill tumor cells. Herein, we describe a potent CDK9 inhibitor, LY2857785, that significantly reduces RNAP II CTD phosphorylation and dramatically decreases MCL1 protein levels to result in apoptosis in a variety of leukemia and solid tumor cell lines. This molecule inhibits the growth of a broad panel of cancer cell lines, and is particularly efficacious in leukemia cells, including orthotopic leukemia preclinical models as well as in ex vivo acute myeloid leukemia and chronic lymphocytic leukemia patient tumor samples. Thus, inhibition of CDK9 may represent an interesting approach as a cancer therapeutic target, especially in hematologic malignancies. Mol Cancer Ther; 13(6); 1442–56. ©2014 AACR.
Cell Death And SenescenceTranscriptional control of apoptosisCell SignalingProtein serine-threonine kinasesComputational MethodsGene expression profilingDrug Discovery TechnologiesStructural studiesDrug MechanismsCellular responses to anticancer drugsDrug TargetsProtein kinase & phosphatase drug targetsGene RegulationMechanisms of transcriptionPhosphorylation and gene expressionHematological CancersLeukemiasSmall Molecule Agents