5UP3

Structure-Based Design of ASK1 Inhibitors as Potential First-in-Class Agents for Heart Failure

5UP3 の概要

• エントリーDOI: 10.2210/pdb5up3/pdb
• 関連するPDBエントリー: 5UOR 5UOX
• 分子名称: Mitogen-activated protein kinase kinase kinase 5, 2-{6-[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]pyridin-2-yl}-2,3-dihydro-1H-isoindol-1-one (3 entities in total)
• 機能のキーワード: transferase, metal-binding, apoptosis, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Cytoplasm: Q99683
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 61658.52

構造登録者

Dougan, D.R. (登録日: 2017-02-01, 公開日: 2017-06-07, 最終更新日: 2024-03-06)

主引用文献

Lanier, M.,Pickens, J.,Bigi, S.V.,Bradshaw-Pierce, E.L.,Chambers, A.,Cheruvallath, Z.S.,Cole, D.,Dougan, D.R.,Ermolieff, J.,Gibson, T.,Halkowycz, P.,Hirokawa, A.,Ivetac, A.,Miura, J.,Nunez, E.,Sabat, M.,Tyhonas, J.,Wang, H.,Wang, X.,Swann, S.
Structure-Based Design of ASK1 Inhibitors as Potential Agents for Heart Failure.
ACS Med Chem Lett, 8:316-320, 2017

PubMed Abstract: Apoptosis signal-regulating kinase 1 (ASK1/MAP3K) is a mitogen-activated protein kinase family member shown to contribute to acute ischemia/reperfusion injury. Using structure-based drug design, deconstruction, and reoptimization of a known ASK1 inhibitor, a lead compound was identified. This compound displayed robust MAP3K pathway inhibition and reduction of infarct size in an isolated perfused heart model of cardiac injury.

PubMed: 28337323
DOI: 10.1021/acsmedchemlett.6b00481

実験手法

X-RAY DIFFRACTION (2.95 Å)