4MXC
Crystal structure of CMET in complex with novel inhibitor
Summary for 4MXC
| Entry DOI | 10.2210/pdb4mxc/pdb |
| Descriptor | Hepatocyte growth factor receptor, N-(3-fluoro-4-{[2-({3-[(methylsulfonyl)methyl]phenyl}amino)pyrimidin-4-yl]oxy}phenyl)-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (3 entities in total) |
| Functional Keywords | cmet inhibitor, transferase-transferase inhibitor complex, transferase/transferase inhibitor |
| Biological source | Homo sapiens (human) |
| Cellular location | Membrane; Single-pass type I membrane protein. Isoform 3: Secreted: P08581 |
| Total number of polymer chains | 1 |
| Total formula weight | 36627.19 |
| Authors | Liu, Q.F.,Chen, T.T.,Xu, Y.C. (deposition date: 2013-09-26, release date: 2014-10-15, Last modification date: 2024-03-20) |
| Primary citation | Zhan, Z.S.,Ai, J.,Liu, Q.F.,Ji, Y.C.,Chen, T.T.,Xu, Y.C.,Geng, M.Y.,Duan, W.H. Discovery of Anilinopyrimidines as Dual Inhibitors of c-Met and VEGFR-2: Synthesis, SAR, and Cellular Activity ACS MED.CHEM.LETT., 5:673-678, 2014 Cited by PubMed Abstract: Both c-Met and VEGFR-2 are important targets for cancer therapies. Here we report a series of potent dual c-Met and VEGFR-2 inhibitors bearing an anilinopyrimidine scaffold. Two novel synthetic protocols were employed for rapid analoguing of the designed molecules for structure-activity relationship (SAR) exploration. Some analogues displayed nanomolar potency against c-Met and VEGFR-2 at enzymatic level. Privileged compounds 3a, 3b, 3g, 3h, and 18a exhibited potent antiproliferative effect against c-Met addictive cell lines with IC50 values ranged from 0.33 to 1.7 μM. In addition, a cocrystal structure of c-Met in complex with 3h has been determined, which reveals the binding mode of c-Met to its inhibitor and helps to interpret the SAR of the analogues. PubMed: 24944742DOI: 10.1021/ml500066m PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (1.632 Å) |
Structure validation
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