3PRE

Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.

3PRE の概要

• エントリーDOI: 10.2210/pdb3pre/pdb
• 関連するPDBエントリー: 3ML8 3ML9 3OAW 3PRZ 3PS6
• 分子名称: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma isoform, 2-amino-8-(trans-4-methoxycyclohexyl)-4-methyl-6-(1H-pyrazol-3-yl)pyrido[2,3-d]pyrimidin-7(8H)-one (2 entities in total)
• 機能のキーワード: phosphoinositide kinase, 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: 111081.51

構造登録者

Knighton, D.R.,Greasley, S.E.,Rodgers, C.M.-L. (登録日: 2010-11-29, 公開日: 2011-02-09, 最終更新日: 2024-02-21)

主引用文献

Liu, K.K.,Huang, X.,Bagrodia, S.,Chen, J.H.,Greasley, S.,Cheng, H.,Sun, S.,Knighton, D.,Rodgers, C.,Rafidi, K.,Zou, A.,Xiao, J.,Yan, S.
Quinazolines with intra-molecular hydrogen bonding scaffold (iMHBS) as PI3K/mTOR dual inhibitors.
Bioorg.Med.Chem.Lett., 21:1270-1274, 2011

PubMed Abstract: Intra-molecular hydrogen bonding was introduced to the quinazoline motif to form a pseudo ring (intra-molecular H-bond scaffold, iMHBS) to mimic our previous published core structures, pyrido[2.3-D]pyrimidin-7-one and pteridinone, as PI3K/mTOR dual inhibitors. This design results in potent PI3K/mTOR dual inhibitors and the purposed intra-molecular hydrogen bonding structure is well supported by co-crystal structure in PI3Kγ enzyme. In addition, a novel synthetic route was developed for these analogs.

PubMed: 21269826
DOI: 10.1016/j.bmcl.2010.12.026

実験手法

X-RAY DIFFRACTION (2.91 Å)