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4HLE

Compound 21 (1-alkyl-substituted 1,2,4-triazoles)

4HLE の概要
エントリーDOI10.2210/pdb4hle/pdb
分子名称Phosphatidylinositol 4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, 2-[1-(propan-2-yl)-1H-1,2,4-triazol-5-yl]-4,5-dihydrothieno[3,2-d][1]benzoxepine-8-carboxamide (2 entities in total)
機能のキーワードlipid kinase, kinase, transferase-transferase inhibitor complex, transferase/transferase inhibitor
由来する生物種Homo sapiens (human)
細胞内の位置Cytoplasm: P48736
タンパク質・核酸の鎖数1
化学式量合計111081.53
構造登録者
Murray, J.M.,Rouge, L.,Wu, P. (登録日: 2012-10-16, 公開日: 2013-01-09, 最終更新日: 2024-02-28)
主引用文献Staben, S.T.,Blaquiere, N.,Tsui, V.,Kolesnikov, A.,Do, S.,Bradley, E.K.,Dotson, J.,Goldsmith, R.,Heffron, T.P.,Lesnick, J.,Lewis, C.,Murray, J.,Nonomiya, J.,Olivero, A.G.,Pang, J.,Rouge, L.,Salphati, L.,Wei, B.,Wiesmann, C.,Wu, P.
Cis-Amide isosteric replacement in thienobenzoxepin inhibitors of PI3-kinase.
Bioorg.Med.Chem.Lett., 23:897-901, 2013
Cited by
PubMed Abstract: Substructural class effects surrounding replacement of a 'cis' N-methyl aniline amide within potent and selective thienobenzoxepin PI3-kinase inhibitors are disclosed. While a simple aryl to alkyl switch was not tolerated due to differences in preferred amide conformation, heterocyclic amide isosteres with maintained aryl substitution improved potency and metabolic stability at the cost of physical properties. These gains in potency allowed lipophilic deconstruction of the arene to simple branched alkyl substituents. As such, overall lipophilicity-neutral, MW decreases were realized relative to the aniline amide series. The improved properties for lead compound 21 resulted in high permeability, solubility and bioavailability.
PubMed: 23265894
DOI: 10.1016/j.bmcl.2012.10.121
主引用文献が同じPDBエントリー
実験手法
X-RAY DIFFRACTION (2.78 Å)
構造検証レポート
Validation report summary of 4hle
検証レポート(詳細版)ダウンロードをダウンロード

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件を2024-11-06に公開中

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