5G55

3-Quinoline Carboxamides inhibitors of Pi3K

5G55 の概要

• エントリーDOI: 10.2210/pdb5g55/pdb
• 分子名称: PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE 3-KINASE CATALYTIC SUBUNIT GAMMA ISOFORM, 6-cyano-4-[[(1R)-1-(4-methylphenyl)ethyl]amino]quinoline-3-carboxamide, SULFATE ION, ... (4 entities in total)
• 機能のキーワード: transferase, atm
• 由来する生物種: HOMO SAPIENS
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 111182.61

構造登録者

Edman, K.,Phillips, C. (登録日: 2016-05-20, 公開日: 2016-08-03, 最終更新日: 2024-05-08)

主引用文献

Degorce, S.L.,Barlaam, B.,Cadogan, E.,Dishington, A.P.,Ducray, R.,Glossop, S.C.,Hassall, L.A.,Lach, F.,Lau, A.,Mcguire, T.M.,Nowak, T.,Ouvry, G.,Pike, K.G.,Thomason, A.G.
Discovery of Novel 3-Quinoline Carboxamides as Potent, Selective and Orally Bioavailable Inhibitors of Ataxia Telangiectasia Mutated (Atm) Kinase.
J.Med.Chem., 59:6281-, 2016

PubMed Abstract: A novel series of 3-quinoline carboxamides has been discovered and optimized as selective inhibitors of the ataxia telangiectasia mutated (ATM) kinase. From a modestly potent HTS hit (4), we identified molecules such as 6-[6-(methoxymethyl)-3-pyridinyl]-4-{[(1R)-1-(tetrahydro-2H-pyran-4-yl)ethyl]amino}-3-quinolinecarboxamide (72) and 7-fluoro-6-[6-(methoxymethyl)pyridin-3-yl]-4-{[(1S)-1-(1-methyl-1H-pyrazol-3-yl)ethyl]amino}quinoline-3-carboxamide (74) as potent and highly selective ATM inhibitors with overall ADME properties suitable for oral administration. 72 and 74 constitute excellent oral tools to probe ATM inhibition in vivo. Efficacy in combination with the DSB-inducing agent irinotecan was observed in a disease relevant model.

PubMed: 27259031
DOI: 10.1021/ACS.JMEDCHEM.6B00519

実験手法

X-RAY DIFFRACTION (2.45 Å)