6VRE

Structure of ASK1 bound to BIO-1772961

6VRE の概要

• エントリーDOI: 10.2210/pdb6vre/pdb
• 分子名称: Mitogen-activated protein kinase kinase kinase 5, DIMETHYL SULFOXIDE, 3-methoxy-N-{6-[4-(propan-2-yl)-4H-1,2,4-triazol-3-yl]pyridin-2-yl}-1-(pyrazin-2-yl)-1H-pyrazole-4-carboxamide, ... (4 entities in total)
• 機能のキーワード: ask1, kinase domain, transferase
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 66415.67

構造登録者

Chodaparambil, J.V.,Marcotte, D.J. (登録日: 2020-02-07, 公開日: 2020-05-06, 最終更新日: 2023-10-11)

主引用文献

Xin, Z.,Himmelbauer, M.K.,Jones, J.H.,Enyedy, I.,Gilfillan, R.,Hesson, T.,King, K.,Marcotte, D.J.,Murugan, P.,Santoro, J.C.,Gonzalez-Lopez de Turiso, F.
Discovery of CNS-Penetrant Apoptosis Signal-Regulating Kinase 1 (ASK1) Inhibitors.
Acs Med.Chem.Lett., 11:485-490, 2020

PubMed Abstract: Apoptosis signal-regulating kinase 1 (ASK1) is a key mediator in the apoptotic and inflammatory cellular stress response. To investigate the therapeutic value of modulating this pathway in neurological disease, we have completed medicinal chemistry studies to identify novel CNS-penetrant ASK1 inhibitors starting from peripherally restricted compounds reported in the literature. This effort led to the discovery of , a novel ASK1 inhibitor with good potency (cell IC = 138 nM), low clearance (rat Cl/Cl = 0.36/6.7 L h kg) and good CNS penetration (rat = 0.38).

PubMed: 32292554
DOI: 10.1021/acsmedchemlett.9b00611

実験手法

X-RAY DIFFRACTION (2.29 Å)