Selective degradation of CDK6 by a palbociclib based PROTAC

Sandeep Rana, Mourad Bendjennat, Smit Kour, Hannah M. King, Smitha Kizhake, Muhammad Zahid, Amarnath Natarajan

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Development of selective kinase inhibitors that target the ATP binding site continues to be a challenge largely due to similar binding pockets. Palbociclib is a cyclin-dependent kinase inhibitor that targets the ATP binding site of CDK4 and CDK6 with similar potency. The enzymatic function associated with the kinase can be effectively probed using kinase inhibitors however the kinase-independent functions cannot. Herein, we report a palbociclib based PROTAC that selectively degrades CDK6 while sparing the homolog CDK4. We used competition studies to characterize the binding and mechanism of CDK6 degradation.

Original languageEnglish (US)
Pages (from-to)1375-1379
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume29
Issue number11
DOIs
StatePublished - Jun 1 2019

Fingerprint

Phosphotransferases
Degradation
Adenosine Triphosphate
Binding Sites
Cyclin-Dependent Kinases
palbociclib

Keywords

  • CDK6
  • CDK6 degrader
  • PROTAC
  • Palbociclib

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

Cite this

Selective degradation of CDK6 by a palbociclib based PROTAC. / Rana, Sandeep; Bendjennat, Mourad; Kour, Smit; King, Hannah M.; Kizhake, Smitha; Zahid, Muhammad; Natarajan, Amarnath.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 29, No. 11, 01.06.2019, p. 1375-1379.

Research output: Contribution to journalArticle

Rana, Sandeep ; Bendjennat, Mourad ; Kour, Smit ; King, Hannah M. ; Kizhake, Smitha ; Zahid, Muhammad ; Natarajan, Amarnath. / Selective degradation of CDK6 by a palbociclib based PROTAC. In: Bioorganic and Medicinal Chemistry Letters. 2019 ; Vol. 29, No. 11. pp. 1375-1379.
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