Ferguson, Fleur M. Doctor, Zainab M. Ficarro, Scott B. Browne, Christopher M. Marto, Jarrod A. Johnson, Jared L. Yaron, Tomer M. Cantley, Lewis C. Kim, Nam Doo Sim, Taebo Berberich, Matthew J. Kalocsay, Marian Sorger, Peter K. Gray, Nathanael S. 2024-01-19T20:00:53Z 2024-01-19T20:00:53Z 2022-01-25 2019-06 2451-9448 https://pubs.kist.re.kr/handle/201004/119898 Cyclin-dependent kinase 14 (CDK14) and other TAIRE family kinases (CDKs 15-18) are proteins that lack functional annotation but are frequent off-targets of clinical kinase inhibitors. In this study we develop and characterize FMF-04-159-2, a tool compound that specifically targets CDK14 covalently and possesses a TAIRE kinase-biased selectivity profile. This tool compound and its reversible analog were used to characterize the cellular consequences of covalent CDK14 inhibition, including an unbiased investigation using phospho-proteomics. To reduce confounding off-target activity, washout conditions were used to deconvolute CDK14-specific effects. This investigation suggested that CDK14 plays a supporting role in cell-cycle regulation, particularly mitotic progression, and identified putative CDK14 substrates. Together, these results represent an important step forward in understanding the cellular consequences of inhibiting CDK14 kinase activity. English CELL PRESS Discovery of Covalent CDK14 Inhibitors with Pan-TAIRE Family Specificity Article 10.1016/j.chembiol.2019.02.015 1 CELL CHEMICAL BIOLOGY, v.26, no.6, pp.804 - + CELL CHEMICAL BIOLOGY 26 6 804 + N scie scopus 000472159700004 2-s2.0-85066461252 Biochemistry & Molecular Biology Biochemistry & Molecular Biology Article IDENTIFICATION TARGET PFTK1 PHOSPHORYLATION PROLIFERATION PATHWAYS PROTEINS INVASION KINASES POTENT CDK14 cell cycle covalent inhibitor druggable genome mitosis TAIRE kinase