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Bioorg Med Chem Lett. 2013 Oct 15;23(20):5578-85. doi: 10.1016/j.bmcl.2013.08.046. Epub 2013 Aug 16.

A Casein kinase 1/Checkpoint kinase 1 pyrazolo-pyridine protein kinase inhibitor as novel activator of the p53 pathway.

Author information

1
p53 Signal Transduction Group, University of Edinburgh Cancer Research Centre in the Institute of Genetics and Molecular Medicine, Crewe Road South, Edinburgh EH4 2XR, United Kingdom.

Abstract

Reactivation of the wild-type p53 pathway is one key goal aimed at developing targeted therapeutics in the cancer research field. Although most p53 protein kinases form 'p53-activating' signals, there are few kinases whose action can contribute to the inhibition of p53, as Casein kinase 1 (CK1) and Checkpoint kinase 1 (CHK1). Here we report on a pyrazolo-pyridine analogue showing activity against both CK1 and CHK1 kinases that lead to p53 pathway stabilisation, thus having pharmacological similarities to the p53-activator Nutlin-3. These data demonstrate the emerging potential utility of multivalent kinase inhibitors.

KEYWORDS:

Casein kinase 1; Checkpoint kinase 1; Kinase inhibitor; p53 Pathway activation

PMID:
24007918
DOI:
10.1016/j.bmcl.2013.08.046
[Indexed for MEDLINE]

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