4LWV

The 2.3A Crystal Structure of Humanized Xenopus MDM2 with RO5545353

4LWV の概要

• エントリーDOI: 10.2210/pdb4lwv/pdb
• 関連するPDBエントリー: 4LWT 4LWU
• 分子名称: 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)
• 機能のキーワード: mdm2, 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: 3
• 化学式量合計: 31641.05

構造登録者

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

主引用文献

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

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: 24900784
DOI: 10.1021/ml400359z

実験手法

X-RAY DIFFRACTION (2.32 Å)