4LWV
The 2.3A Crystal Structure of Humanized Xenopus MDM2 with RO5545353
Summary for 4LWV
| Entry DOI | 10.2210/pdb4lwv/pdb |
| Related | 4LWT 4LWU |
| Descriptor | E3 ubiquitin-protein ligase Mdm2, (2S,3R,4R,5R)-N-(4-carbamoyl-2-methoxyphenyl)-2'-chloro-4-(3-chloro-2-fluorophenyl)-2-(2,2-dimethylpropyl)-5'-oxo-4',5'-dihydrospiro[pyrrolidine-3,6'-thieno[3,2-b]pyrrole]-5-carboxamide, SULFATE ION, ... (4 entities in total) |
| Functional Keywords | mdm2, 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 | 3 |
| Total formula weight | 31641.05 |
| Authors | Graves, B.J.,Lukacs, C.,Janson, C.A. (deposition date: 2013-07-28, release date: 2014-07-02, Last modification date: 2024-02-28) |
| Primary citation | Zhang, Z.,Chu, X.J.,Liu, J.J.,Ding, Q.,Zhang, J.,Bartkovitz, D.,Jiang, N.,Karnachi, P.,So, S.S.,Tovar, C.,Filipovic, Z.M.,Higgins, B.,Glenn, K.,Packman, K.,Vassilev, L.,Graves, B. Discovery of Potent and Orally Active p53-MDM2 Inhibitors RO5353 and RO2468 for Potential Clinical Development. ACS MED.CHEM.LETT., 5:124-127, 2014 Cited by PubMed Abstract: The development of small-molecule MDM2 inhibitors to restore dysfunctional p53 activities represents a novel approach for cancer treatment. In a previous communication, the efforts leading to the identification of a non-imidazoline MDM2 inhibitor, RG7388, was disclosed and revealed the desirable in vitro and in vivo pharmacological properties that this class of pyrrolidine-based inhibitors possesses. Given this richness and the critical need for a wide variety of chemical structures to ensure success in the clinic, research was expanded to evaluate additional derivatives. Here we report two new potent, selective, and orally active p53-MDM2 antagonists, RO5353 and RO2468, as follow-ups with promising potential for clinical development. PubMed: 24900784DOI: 10.1021/ml400359z PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2.32 Å) |
Structure validation
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