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

doi:10.1039/c7cc03879h

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 journal › Article › peer-review

192 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 language	English (US)
Pages (from-to)	7577-7580
Number of pages	4
Journal	Chemical Communications
Volume	53
Issue number	54
DOIs	https://doi.org/10.1039/c7cc03879h
State	Published - 2017

ASJC Scopus subject areas

Electronic, Optical and Magnetic Materials
Catalysis
Ceramics and Composites
General Chemistry
Surfaces, Coatings and Films
Metals and Alloys
Materials Chemistry

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10.1039/c7cc03879h

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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.",

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T1 - Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC)

AU - Robb, Caroline M.

AU - Contreras, Jacob I.

AU - Kour, Smit

AU - Taylor, Margaret A.

AU - Abid, Mohammad

AU - Sonawane, Yogesh A.

AU - Zahid, Muhammad

AU - Murry, Daryl J

AU - Natarajan, Amarnath

AU - Rana, Sandeep

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

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

Abstract

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