6GGN
In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor
Summary for 6GGN
| Entry DOI | 10.2210/pdb6ggn/pdb |
| Descriptor | E3 ubiquitin-protein ligase Mdm2, (4~{S})-4-(4-chloranyl-2-methyl-phenyl)-5-(5-chloranyl-2-methyl-phenyl)-2-(2,4-dimethoxypyrimidin-5-yl)-3-propan-2-yl-4~{H}-pyrrolo[3,4-d]imidazol-6-one, CHLORIDE ION, ... (4 entities in total) |
| Functional Keywords | ppi with p53, inhibitor complex, cell cycle |
| Biological source | Homo sapiens (Human) |
| Total number of polymer chains | 1 |
| Total formula weight | 11743.96 |
| Authors | Kallen, J. (deposition date: 2018-05-03, release date: 2018-09-26, Last modification date: 2024-01-17) |
| Primary citation | Vaupel, A.,Holzer, P.,Ferretti, S.,Guagnano, V.,Kallen, J.,Mah, R.,Masuya, K.,Ruetz, S.,Rynn, C.,Schlapbach, A.,Stachyra, T.,Stutz, S.,Todorov, M.,Jeay, S.,Furet, P. In vitro and in vivo characterization of a novel, highly potent p53-MDM2 inhibitor. Bioorg. Med. Chem. Lett., 28:3404-3408, 2018 Cited by PubMed Abstract: Small molecule inhibitors of the p53-MDM2 protein complex are under intense investigation in clinical trials as anti-cancer agents, including our first generation inhibitor NVP-CGM097. We recently described the rational design of a novel pyrazolopyrrolidinone core as a new lead structure and now we report on the synthesis and optimization of this to provide a highly potent lead compound. This new compound displayed excellent oral efficacy in our preclinical mechanistic in vivo model and marked a significant milestone towards the identification of our second generation clinical candidate NVP-HDM201. PubMed: 30217415DOI: 10.1016/j.bmcl.2018.08.027 PDB entries with the same primary citation |
| Experimental method | X-RAY DIFFRACTION (2 Å) |
Structure validation
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