4JSC

The 2.5A crystal structure of humanized Xenopus MDM2 with RO5316533 - a pyrrolidine MDM2 inhibitor

4JSC の概要

• エントリーDOI: 10.2210/pdb4jsc/pdb
• 関連するPDBエントリー: 4IPF 4JRG
• 分子名称: 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)
• 機能のキーワード: pyrrolidine, ligase-antagonist complex, e3 ubiquitin ligase, p53, nucleus, ligase-ligase inhibitor complex, ligase/ligase inhibitor
• 由来する生物種: Xenopus laevis (clawed frog,common platanna,platanna)
• 細胞内の位置: Nucleus, nucleoplasm (By similarity): P56273
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 21034.14

構造登録者

Janson, C.A.,Lukacs, C.,Graves, B. (登録日: 2013-03-22, 公開日: 2013-07-24, 最終更新日: 2024-02-28)

主引用文献

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

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: 23808545
DOI: 10.1021/jm400487c

実験手法

X-RAY DIFFRACTION (2.5 Å)