4DHF
Structure of Aurora A mutant bound to Biogenidec cpd 15
Summary for 4DHF
| Entry DOI | 10.2210/pdb4dhf/pdb |
| Related | 3R21 3R22 |
| Descriptor | Aurora kinase A, 7-cyclopentyl-2-({1-methyl-5-[(4-methylpiperazin-1-yl)carbonyl]-1H-pyrrol-3-yl}amino)-7H-pyrrolo[2,3-d]pyrimidine-6-carboxamide, PHOSPHATE ION, ... (4 entities in total) |
| Functional Keywords | ser/thr kinase mitotic kinase pyrazolopyrimidine, phosphorylation, tpx2, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Cytoplasm, cytoskeleton, centrosome: O14965 |
| Total number of polymer chains | 2 |
| Total formula weight | 63833.50 |
| Authors | Silvian, L.,Marcotte, D.J. (deposition date: 2012-01-27, release date: 2012-07-18, Last modification date: 2024-02-28) |
| Primary citation | Le Brazidec, J.Y.,Pasis, A.,Tam, B.,Boykin, C.,Wang, D.,Marcotte, D.J.,Claassen, G.,Chong, J.H.,Chao, J.,Fan, J.,Nguyen, K.,Silvian, L.,Ling, L.,Zhang, L.,Choi, M.,Teng, M.,Pathan, N.,Zhao, S.,Li, T.,Taveras, A. Structure-based design of 2,6,7-trisubstituted-7H-pyrrolo[2,3-d]pyrimidines as Aurora kinases inhibitors. Bioorg.Med.Chem.Lett., 22:4033-4037, 2012 Cited by PubMed Abstract: This Letter reports the optimization of a pyrrolopyrimidine series as dual inhibitors of Aurora A/B kinases. This series derived from a pyrazolopyrimidine series previously reported as inhibitors of aurora kinases and CDKs. In an effort to improve the selectivity of this chemotype, we switched to the pyrrolopyrimidine core which allowed functionalization on C-2. In addition, the modeling rationale was based on superimposing the structures of Aurora-A kinase and CDK2 which revealed enough differences leading to a path for selectivity improvement. The synthesis of the new series of pyrrolopyrimidine analogs relied on the development of a different route for the two key intermediates 7 and 19 which led to analogs with both tunable activity against CDK1 and maintained cell potency. PubMed: 22607669DOI: 10.1016/j.bmcl.2012.04.085 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.8 Å) |
Structure validation
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