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Bioorg Med Chem Lett. 2019 Aug 1;29(15):1985-1993. doi: 10.1016/j.bmcl.2019.05.024. Epub 2019 May 23.

Synthesis and structure activity relationships of a series of 4-amino-1H-pyrazoles as covalent inhibitors of CDK14.

Author information

1
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02215, USA.
2
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA.
3
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Blais Proteomics Center, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Department of Pathology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02215, USA; Department of Oncologic Pathology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
4
Daegu-Gyeongbuk Medical Innovation Foundation, Republic of Korea.
5
Chemical Kinomics Research Center, Korea Institute of Science and Technology, Republic of Korea; KU-KIST Graduate School of Converging Science and Technology, Korea University, Republic of Korea.
6
Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: nathanael_gray@dfci.harvard.edu.

Abstract

The TAIRE family of kinases are an understudied branch of the CDK kinase family, that have been implicated in a number of cancers. This manuscript describes the design, synthesis and SAR of covalent CDK14 inhibitors, culminating in identification of FMF-04-159-2, a potent, covalent CDK14 inhibitor with a TAIRE kinase biased selectivity profile.

KEYWORDS:

CDK inhibitor; CDK14; CDK15; CDK16; CDK17; CDK18; Cell cycle; Covalent kinase inhibitor; Mitosis; TAIRE kinase

PMID:
31175010
DOI:
10.1016/j.bmcl.2019.05.024

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