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

45 Citations (Scopus)

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 - Jan 1 2017

Fingerprint

Cyclin-Dependent Kinase 9
Proteolysis
Degradation
Cyclin-Dependent Kinases
Elongation
Genes
Molecules

ASJC Scopus subject areas

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

Cite this

Robb, C. M., Contreras, J. I., Kour, S., Taylor, M. A., Abid, M., Sonawane, Y. 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

Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC). / Robb, Caroline M.; Contreras, Jacob I.; Kour, Smit; Taylor, Margaret A.; Abid, Mohammad; Sonawane, Yogesh A.; Zahid, Muhammad; Murry, Daryl J; Natarajan, Amarnath; Rana, Sandeep.

In: Chemical Communications, Vol. 53, No. 54, 01.01.2017, p. 7577-7580.

Research output: Contribution to journalArticle

Robb, CM, Contreras, JI, Kour, S, Taylor, MA, Abid, M, Sonawane, YA, Zahid, M, Murry, DJ, Natarajan, A & Rana, S 2017, 'Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC)', Chemical Communications, vol. 53, no. 54, pp. 7577-7580. https://doi.org/10.1039/c7cc03879h
Robb CM, Contreras JI, Kour S, Taylor MA, Abid M, Sonawane YA et al. Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC). Chemical Communications. 2017 Jan 1;53(54):7577-7580. https://doi.org/10.1039/c7cc03879h
Robb, Caroline M. ; Contreras, Jacob I. ; Kour, Smit ; Taylor, Margaret A. ; Abid, Mohammad ; Sonawane, Yogesh A. ; Zahid, Muhammad ; Murry, Daryl J ; Natarajan, Amarnath ; Rana, Sandeep. / Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC). In: Chemical Communications. 2017 ; Vol. 53, No. 54. pp. 7577-7580.
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