4JP4

Mmp13 in complex with a reverse hydroxamate Zn-binder

4JP4 の概要

• エントリーDOI: 10.2210/pdb4jp4/pdb
• 関連するPDBエントリー: 4JPA
• 分子名称: Collagenase 3, ZINC ION, CALCIUM ION, ... (6 entities in total)
• 機能のキーワード: matrix metalloprotease, calcium binding, zinc binding, hydrolase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Secreted, extracellular space, extracellular matrix (Probable): P45452
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 40534.29

構造登録者

Gerhardt, S.,Hargreaves, D. (登録日: 2013-03-19, 公開日: 2014-03-05, 最終更新日: 2024-03-20)

主引用文献

De Savi, C.,Waterson, D.,Pape, A.,Lamont, S.,Hadley, E.,Mills, M.,Page, K.M.,Bowyer, J.,Maciewicz, R.A.
Hydantoin based inhibitors of MMP13--discovery of AZD6605.
Bioorg.Med.Chem.Lett., 23:4705-4712, 2013

PubMed Abstract: Piperidine ether and aryl piperazine hydantoins are reported as potent inhibitors of MMP13. A medicinal chemistry campaign focused on replacing the reverse hydroxamate zinc binding group associated with historical inhibitors with a hydantoin zinc binding group then optimising MMP13 potency, solubility and DMPK properties whilst maintaining good selectivity over MMP14. A number of high quality candidates were progressed and following rat and dog safety evaluation, AZD6605 (3m) was identified as a candidate drug.

PubMed: 23810497
DOI: 10.1016/j.bmcl.2013.05.089

実験手法

X-RAY DIFFRACTION (1.43 Å)