4JSC
The 2.5A crystal structure of humanized Xenopus MDM2 with RO5316533 - a pyrrolidine MDM2 inhibitor
Summary for 4JSC
| Entry DOI | 10.2210/pdb4jsc/pdb |
| Related | 4IPF 4JRG |
| Descriptor | E3 ubiquitin-protein ligase Mdm2, (3S,4R,5S)-3-(3-chloro-2-fluorophenyl)-4-(4-chloro-2-fluorophenyl)-4-cyano-N-[(3S)-3,4-dihydroxybutyl]-5-(2,2-dimethylpropyl)-D-prolinamide (3 entities in total) |
| Functional Keywords | pyrrolidine, ligase-antagonist complex, e3 ubiquitin ligase, p53, nucleus, ligase-ligase inhibitor complex, ligase/ligase inhibitor |
| Biological source | Xenopus laevis (clawed frog,common platanna,platanna) |
| Cellular location | Nucleus, nucleoplasm (By similarity): P56273 |
| Total number of polymer chains | 2 |
| Total formula weight | 21034.14 |
| Authors | Janson, C.A.,Lukacs, C.,Graves, B. (deposition date: 2013-03-22, release date: 2013-07-24, Last modification date: 2024-02-28) |
| Primary citation | Ding, Q.,Zhang, Z.,Liu, J.J.,Jiang, N.,Zhang, J.,Ross, T.M.,Chu, X.J.,Bartkovitz, D.,Podlaski, F.,Janson, C.,Tovar, C.,Filipovic, Z.M.,Higgins, B.,Glenn, K.,Packman, K.,Vassilev, L.T.,Graves, B. Discovery of RG7388, a Potent and Selective p53-MDM2 Inhibitor in Clinical Development. J.Med.Chem., 56:5979-5983, 2013 Cited by PubMed Abstract: Restoration of p53 activity by inhibition of the p53-MDM2 interaction has been considered an attractive approach for cancer treatment. However, the hydrophobic protein-protein interaction surface represents a significant challenge for the development of small-molecule inhibitors with desirable pharmacological profiles. RG7112 was the first small-molecule p53-MDM2 inhibitor in clinical development. Here, we report the discovery and characterization of a second generation clinical MDM2 inhibitor, RG7388, with superior potency and selectivity. PubMed: 23808545DOI: 10.1021/jm400487c PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.5 Å) |
Structure validation
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