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

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.

SUBMITTER: Robb CM

PROVIDER: S-EPMC5555382 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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

Robb Caroline M CM Contreras Jacob I JI Kour Smit S Taylor Margaret A MA Abid Mohammad M Sonawane Yogesh A YA Zahid Muhammad M Murry Daryl J DJ Natarajan Amarnath A Rana Sandeep S

Chemical communications (Cambridge, England) 20170701 54

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, ...[more]

PMID: 28636052

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2019-04-26 | GSE98268 | GEO

Disordered region of cereblon is required for efficient degradation by proteolysis-targeting chimera.

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RUNX1 knockdown and BET protein proteolysis targeting chimera (PROTAC) exerts potent lethal activity against mtRUNX1 AML cells

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2020-08-11 | GSE119261 | GEO

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