6AYD

Pim1 complexed with N-(6-(4-hydroxyphenyl)-1H-indazol-3-yl)cyclopropanecarboxamide

6AYD の概要

• エントリーDOI: 10.2210/pdb6ayd/pdb
• 分子名称: Serine/threonine-protein kinase pim-1, N-[6-(4-hydroxyphenyl)-2H-indazol-3-yl]cyclopropanecarboxamide (3 entities in total)
• 機能のキーワード: kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 由来する生物種: Homo sapiens (Human)
• 細胞内の位置: Isoform 2: Cytoplasm. Isoform 1: Cell membrane: P11309
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 38355.47

構造登録者

Shewchuk, L.M.,Henley, Z.A. (登録日: 2017-09-08, 公開日: 2017-12-27, 最終更新日: 2023-10-04)

主引用文献

Henley, Z.A.,Bax, B.D.,Inglesby, L.M.,Champigny, A.,Gaines, S.,Faulder, P.,Le, J.,Thomas, D.A.,Washio, Y.,Baldwin, I.R.
From PIM1 to PI3K delta via GSK3 beta : Target Hopping through the Kinome.
ACS Med Chem Lett, 8:1093-1098, 2017

PubMed Abstract: Selective inhibitors of phosphoinositide 3-kinase delta are of interest for the treatment of inflammatory diseases. Initial optimization of a 3-substituted indazole hit compound targeting the kinase PIM1 focused on improving selectivity over GSK3β through consideration of differences in the ATP binding pockets. Continued kinase cross-screening showed PI3Kδ activity in a series of 4,6-disubstituted indazole compounds, and subsequent structure-activity relationship exploration led to the discovery of an indole-containing lead compound as a potent PI3Kδ inhibitor with selectivity over the other PI3K isoforms.

PubMed: 29057057
DOI: 10.1021/acsmedchemlett.7b00296

実験手法

X-RAY DIFFRACTION (3 Å)