4LWU

The 1.14A Crystal Structure of Humanized Xenopus MDM2 with RO5499252

4LWU の概要

• エントリーDOI: 10.2210/pdb4lwu/pdb
• 関連するPDBエントリー: 4LWT 4LWV
• 分子名称: E3 ubiquitin-protein ligase Mdm2, (2'S,3R,4'S,5'R)-N-(4-carbamoylphenyl)-6-chloro-4'-(3-chloro-2-fluorophenyl)-2'-(2,2-dimethylpropyl)-2-oxo-1,2-dihydrospiro[indole-3,3'-pyrrolidine]-5'-carboxamide, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: mdm2, spiroindolinone, 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: 1
• 化学式量合計: 10510.96

構造登録者

Graves, B.J.,Lukacs, C.,Janson, C.A. (登録日: 2013-07-28, 公開日: 2014-07-16, 最終更新日: 2024-02-28)

主引用文献

Zhang, Z.,Ding, Q.,Liu, J.J.,Zhang, J.,Jiang, N.,Chu, X.J.,Bartkovitz, D.,Luk, K.C.,Janson, C.,Tovar, C.,Filipovic, Z.M.,Higgins, B.,Glenn, K.,Packman, K.,Vassilev, L.T.,Graves, B.
Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy.
Bioorg.Med.Chem., 22:4001-4009, 2014

PubMed Abstract: The field of small-molecule inhibitors of protein-protein interactions is rapidly advancing and the specific area of inhibitors of the p53/MDM2 interaction is a prime example. Several groups have published on this topic and multiple compounds are in various stages of clinical development. Building on the strength of the discovery of RG7112, a Nutlin imidazoline-based compound, and RG7388, a pyrrolidine-based compound, we have developed additional scaffolds that provide opportunities for future development. Here, we report the discovery and optimization of a highly potent and selective series of spiroindolinone small-molecule MDM2 inhibitors, culminating in RO8994.

PubMed: 24997575
DOI: 10.1016/j.bmc.2014.05.072

実験手法

X-RAY DIFFRACTION (1.14 Å)