Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC)

Caroline M. Robb, Jacob I. Contreras, Smit Kour, Margaret A. Taylor, Mohammad Abid, Yogesh A. Sonawane, Muhammad Zahid, Daryl J Murry, Amarnath Natarajan, Sandeep Rana

Research output: Contribution to journalArticle

65 Scopus citations

Abstract

Cyclin-dependent kinase 9 (CDK9), a member of the cyclin-dependent protein kinase (CDK) family, is involved in transcriptional elongation of several target genes. CDK9 is ubiquitously expressed and has been shown to contribute to a variety of malignancies such as pancreatic, prostate and breast cancers. Here we report the development of a heterobifunctional small molecule proteolysis targeting chimera (PROTAC) capable of cereblon (CRBN) mediated proteasomal degradation of CDK9. In HCT116 cells, it selectively degrades CDK9 while sparing other CDK family members. This is the first example of a PROTAC that selectively degrades CDK9.

Original languageEnglish (US)
Pages (from-to)7577-7580
Number of pages4
JournalChemical Communications
Volume53
Issue number54
DOIs
StatePublished - 2017

ASJC Scopus subject areas

  • Catalysis
  • Electronic, Optical and Magnetic Materials
  • Ceramics and Composites
  • Chemistry(all)
  • Surfaces, Coatings and Films
  • Metals and Alloys
  • Materials Chemistry

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    Robb, C. M., Contreras, J. I., Kour, S., Taylor, M. A., Abid, M., Sonawane, Y. A., Zahid, M., Murry, D. J., Natarajan, A., & Rana, S. (2017). Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC). Chemical Communications, 53(54), 7577-7580. https://doi.org/10.1039/c7cc03879h