4AUA
Liganded X-ray crystal structure of cyclin dependent kinase 6 (CDK6)
Summary for 4AUA
| Entry DOI | 10.2210/pdb4aua/pdb |
| Related | 1BI7 1BI8 1BLX 1G3N 1JOW 1XO2 2EUF 2F2C |
| Descriptor | CYCLIN-DEPENDENT KINASE 6, 1H-benzimidazol-2-yl(1H-pyrrol-2-yl)methanone (3 entities in total) |
| Functional Keywords | transferase |
| Biological source | HOMO SAPIENS (HUMAN) |
| Total number of polymer chains | 1 |
| Total formula weight | 35230.43 |
| Authors | Cho, Y.S.,Angove, H.,Brain, C.,Chen, C.H.T.,Cheng, R.,Chopra, R.,Chung, K.,Congreve, M.,Dagostin, C.,Davis, D.,Feltell, R.,Giraldes, J.,Hiscock, S.,Kim, S.,Kovats, S.,Lagu, B.,Lewry, K.,Loo, A.,Lu, Y.,Luzzio, M.,Maniara, W.,Mcmenamin, R.,Mortenson, P.,Benning, R.,O'Reilly, M.,Rees, D.,Shen, J.,Smith, T.,Wang, Y.,Williams, G.,Woolford, A.,Wrona, W.,Xu, M.,Yang, F.,Howard, S. (deposition date: 2012-05-15, release date: 2013-02-06, Last modification date: 2024-05-08) |
| Primary citation | Cho, Y.S.,Angove, H.,Brain, C.,Chen, C.H.,Cheng, H.,Cheng, R.,Chopra, R.,Chung, K.,Congreve, M.,Dagostin, C.,Davis, D.J.,Feltell, R.,Giraldes, J.,Hiscock, S.D.,Kim, S.,Kovats, S.,Lagu, B.,Lewry, K.,Loo, A.,Lu, Y.,Luzzio, M.,Maniara, W.,McMenamin, R.,Mortenson, P.N.,Benning, R.,O'Reilly, M.,Rees, D.C.,Shen, J.,Smith, T.,Wang, Y.,Williams, G.,Woolford, A.J.,Wrona, W.,Xu, M.,Yang, F.,Howard, S. Fragment-Based Discovery of 7-Azabenzimidazoles as Potent, Highly Selective, and Orally Active CDK4/6 Inhibitors. ACS Med Chem Lett, 3:445-449, 2012 Cited by PubMed Abstract: Herein, we describe the discovery of potent and highly selective inhibitors of both CDK4 and CDK6 via structure-guided optimization of a fragment-based screening hit. CDK6 X-ray crystallography and pharmacokinetic data steered efforts in identifying compound 6, which showed >1000-fold selectivity for CDK4 over CDKs 1 and 2 in an enzymatic assay. Furthermore, 6 demonstrated in vivo inhibition of pRb-phosphorylation and oral efficacy in a Jeko-1 mouse xenograft model. PubMed: 24900493DOI: 10.1021/ml200241a PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.31 Å) |
Structure validation
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