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

Anne-Sophie Huart, Barbara Saxty, Andy Merritt, Marta Nekulova, Stephen Lewis, Yide Huang, Borivoj Vojtesek, Catherine Kettleborough, Ted R Hupp

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
Pages (from-to)5578-5585
Number of pages8
JournalBioorganic & Medicinal Chemistry Letters
Volume23
Issue number20
DOIs
Publication statusPublished - 15 Oct 2013

Keywords

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

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