Targeting transcriptional dependencies in cancer using a covalent CDK7 inhibitor (ChIP-Seq)

ABSTRACT: Cyclin-dependent kinase 7 (CDK7) plays a critical role in the general regulation of RNA polymerase II-mediated transcription. However, the absence of selective CDK7 inhibitors has hindered the ability to investigate the consequences of acute and prolonged inhibition of CDK7 under normal and pathological conditions. Here we present the discovery and characterization of the first covalent CDK7 inhibitor, CDK7-IN-1, that has the unprecedented ability to target a unique cysteine residue located outside of the canonical kinase domain, providing an unanticipated means of achieving selectivity for CDK7 amongst the 20 known CDKs. Cancer cell line profiling indicates that a subset of cancer cell lines, including T-cell acute lymphoblastic leukemia (T-ALL), exhibit 100-fold greater sensitivity to

ORGANISM(S): Homo sapiens

SUBMITTER: Richard Young 

PROVIDER: E-GEOD-50622 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress