7OIJ

mPI3Kd in complex with an inhibitor

これはPDB形式変換不可エントリーです。

7OIJ の概要

• エントリーDOI: 10.2210/pdb7oij/pdb
• 分子名称: Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit delta isoform, 6-[[5-[2-[(1S)-1-cyclopropylethyl]-7-(methylsulfamoyl)-1-oxidanylidene-3H-isoindol-5-yl]-4-methyl-1,3-thiazol-2-yl]amino]-N-[3-(dimethylamino)propyl]pyridine-2-carboxamide, SODIUM ION, ... (5 entities in total)
• 機能のキーワード: inhibitor, complex, transferase
• 由来する生物種: Mus musculus (Mouse)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 125619.46

構造登録者

Petersen, J. (登録日: 2021-05-11, 公開日: 2021-07-14, 最終更新日: 2024-05-01)

主引用文献

Perry, M.W.D.,Bjorhall, K.,Bold, P.,Brulls, M.,Borjesson, U.,Carlsson, J.,Chang, H.A.,Chen, Y.,Eriksson, A.,Fihn, B.M.,Fransson, R.,Fredlund, L.,Ge, H.,Huang, H.,Karabelas, K.,Lamm Bergstrom, E.,Lever, S.,Lindmark, H.,Mogemark, M.,Nikitidis, A.,Palmgren, A.P.,Pemberton, N.,Petersen, J.,Rodrigo Blomqvist, M.,Smith, R.W.,Thomas, M.J.,Ullah, V.,Tyrchan, C.,Wennberg, T.,Westin Eriksson, A.,Yang, W.,Zhao, S.,Oster, L.
Discovery of AZD8154, a Dual PI3K gamma delta Inhibitor for the Treatment of Asthma.
J.Med.Chem., 64:8053-8075, 2021

PubMed Abstract: Starting from our previously described PI3Kγ inhibitors, we describe the exploration of structure-activity relationships that led to the discovery of highly potent dual PI3Kγδ inhibitors. We explored changes in two positions of the molecules, including macrocyclization, but ultimately identified a simpler series with the desired potency profile that had suitable physicochemical properties for inhalation. We were able to demonstrate efficacy in a rat ovalbumin challenge model of allergic asthma and in cells derived from asthmatic patients. The optimized compound, AZD8154, has a long duration of action in the lung and low systemic exposure coupled with high selectivity against off-targets.

PubMed: 34080862
DOI: 10.1021/acs.jmedchem.1c00434

実験手法

X-RAY DIFFRACTION (1.8 Å)