3OAW

4-Methylpteridineones as Orally Active and Selective PI3K/mTOR Dual Inhibitors

3OAW の概要

• エントリーDOI: 10.2210/pdb3oaw/pdb
• 関連するPDBエントリー: 3ML8 3ML9
• 分子名称: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, 2-amino-4-methyl-8-(1-methylethyl)-6-(1H-pyrazol-4-yl)pteridin-7(8H)-one (3 entities in total)
• 機能のキーワード: phosphoinositide kinase, transferase-transferase, inhibition, inhibitor complex., transferase-transferase inhibitor complex, transferase/transferase inhibitor
• 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: 111012.41

構造登録者

Knighton, D.R.,Greasley, S.E.,Rodgers, C.M.-L. (登録日: 2010-08-05, 公開日: 2010-09-22, 最終更新日: 2024-02-21)

主引用文献

Liu, K.K.,Bagrodia, S.,Bailey, S.,Cheng, H.,Chen, H.,Gao, L.,Greasley, S.,Hoffman, J.E.,Hu, Q.,Johnson, T.O.,Knighton, D.,Liu, Z.,Marx, M.A.,Nambu, M.D.,Ninkovic, S.,Pascual, B.,Rafidi, K.,Rodgers, C.M.,Smith, G.L.,Sun, S.,Wang, H.,Yang, A.,Yuan, J.,Zou, A.
4-methylpteridinones as orally active and selective PI3K/mTOR dual inhibitors.
Bioorg.Med.Chem.Lett., 20:6096-6099, 2010

PubMed Abstract: Pteridinones were designed based on a non-selective kinase template. Because of the uniqueness of the PI3K and mTOR binding pockets, a methyl group was introduced to C-4 position of the peteridinone core to give compounds with excellent selectivity for PI3K and mTOR. This series of compounds were further optimized to improve their potency against PI3Kα and mTOR. Finally, orally active compounds with improved solubility and robust in vivo efficacy in tumor growth inhibition were identified as well.

PubMed: 20817449
DOI: 10.1016/j.bmcl.2010.08.045

実験手法

X-RAY DIFFRACTION (2.75 Å)