| http://purl.uniprot.org/citations/29266803 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/29266803 | http://www.w3.org/2000/01/rdf-schema#comment | "Cyclin-dependent kinase (CDK) 12 knockdown via siRNA decreases the transcription of DNA-damage-response genes and sensitizes BRCA wild-type cells to poly(ADP-ribose) polymerase (PARP) inhibition. To recapitulate this effect with a small molecule, we sought a potent, selective CDK12 inhibitor. Crystal structures and modeling informed hybridization between dinaciclib and SR-3029, resulting in lead compound 5 [(S)-2-(1-(6-(((6,7-difluoro-1H-benzo[d]imidazol-2-yl)methyl)amino)-9-ethyl-9H-purin-2-yl)piperidin-2-yl)ethan-1-ol]. Further structure-guided optimization delivered a series of selective CDK12 inhibitors, including compound 7 [(S)-2-(1-(6-(((6,7-difluoro-1H-benzo[d]imidazol-2-yl)methyl)amino)-9-isopropyl-9H-purin-2-yl)piperidin-2-yl)ethan-1-ol]. Profiling of this compound across CDK9, 7, 2, and 1 at high ATP concentration, single-point kinase panel screening against 352 targets at 0.1 μm, and proteomics via kinase affinity matrix technology demonstrated the selectivity. This series of compounds inhibits phosphorylation of Ser2 on the C-terminal repeat domain of RNA polymerase II, consistent with CDK12 inhibition. These selective compounds were also acutely toxic to OV90 as well as THP1 cells."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.org/dc/terms/identifier | "doi:10.1002/cmdc.201700695"xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Liu Y."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Li S."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Li X."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Zhu X."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Jones N.H."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Wu A."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Su N."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Yao T."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Gao N."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Ferguson A.D."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "O'Connell N."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Tomlinson R."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Prince D.B."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Nguyen T.B."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Rivers E."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Guichard S."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Lamb M.L."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Denz C.R."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Manchester J.I."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Haddrick M."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Cidado J."xsd:string |
| http://purl.uniprot.org/citations/29266803 | http://purl.uniprot.org/core/author | "Johannes J.W."xsd:string |