5UBR

CRYSTAL STRUCTURE OF PI3K ALPHA IN COMPLEX WITH A 7-(3-(PIPERAZIN-1-YL)PHENYL)PYRROLO[2,1-F][1,2,4] TRIAZIN-4-AMINE DERIVIATINE

5UBR の概要

• エントリーDOI: 10.2210/pdb5ubr/pdb
• 関連するPDBエントリー: 5ubt
• 分子名称: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit alpha isoform, 1-[4-(3-{4-amino-5-[1-(oxan-4-yl)-1H-pyrazol-5-yl]pyrrolo[2,1-f][1,2,4]triazin-7-yl}phenyl)piperazin-1-yl]ethan-1-one (3 entities in total)
• 機能のキーワード: lipid kinase, inhibitor, pi3k alpha, transferase-transferase inhibitor complex, transferase-transferase regulator complex, transferase/transferase regulator
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 110283.45

構造登録者

Sack, J.S. (登録日: 2016-12-21, 公開日: 2017-02-08, 最終更新日: 2024-03-06)

主引用文献

Qin, L.Y.,Ruan, Z.,Cherney, R.J.,Dhar, T.G.,Neels, J.,Weigelt, C.A.,Sack, J.S.,Srivastava, A.S.,Cornelius, L.A.,Tino, J.A.,Stefanski, K.,Gu, X.,Xie, J.,Susulic, V.,Yang, X.,Yarde-Chinn, M.,Skala, S.,Bosnius, R.,Goldstein, C.,Davies, P.,Ruepp, S.,Salter-Cid, L.,Bhide, R.S.,Poss, M.A.
Discovery of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent and selective PI3K delta inhibitors.
Bioorg. Med. Chem. Lett., 27:855-861, 2017

PubMed Abstract: As demonstrated in preclinical animal models, the disruption of PI3Kδ expression or its activity leads to a decrease in inflammatory and immune responses. Therefore, inhibition of PI3Kδ may provide an alternative treatment for autoimmune diseases, such as RA, SLE, and respiratory ailments. Herein, we disclose the identification of 7-(3-(piperazin-1-yl)phenyl)pyrrolo[2,1-f][1,2,4]triazin-4-amine derivatives as highly potent, selective and orally bioavailable PI3Kδ inhibitors. The lead compound demonstrated efficacy in an in vivo mouse KLH model.

PubMed: 28108251
DOI: 10.1016/j.bmcl.2017.01.016

実験手法

X-RAY DIFFRACTION (2.4 Å)