7N91

P70 S6K1 IN COMPLEX WITH MSC2317067A-1

7N91 の概要

• エントリーDOI: 10.2210/pdb7n91/pdb
• 分子名称: Ribosomal protein S6 kinase beta-1, 4-{[(1S)-1-(3-fluorophenyl)-2-(methylamino)ethyl]amino}quinazoline-8-carboxamide (2 entities in total)
• 機能のキーワード: kinase domain, inhibitor, transferase, transferase-inhibitor complex, transferase/inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 77771.25

構造登録者

Mochalkin, I. (登録日: 2021-06-16, 公開日: 2022-07-06, 最終更新日: 2024-10-23)

主引用文献

DeSelm, L.,Huck, B.,Lan, R.,Neagu, C.,Potnick, J.,Xiao, Y.,Chen, X.,Jones, R.,Richardson, T.E.,Heasley, B.H.,Haxell, T.,Moore, J.,Tian, H.,Georgi, K.,Rohdich, F.,Sutton, A.,Johnson, T.,Mochalkin, I.,Jackson, J.,Lin, J.,Crowley, L.,Machl, A.,Clark, A.,Wilker, E.,Sherer, B.,Goutopoulos, A.
Identification of Clinical Candidate M2698, a Dual p70S6K and Akt Inhibitor, for Treatment of PAM Pathway-Altered Cancers.
J.Med.Chem., 64:14603-14619, 2021

PubMed Abstract: Herein, we report the discovery of a novel class of quinazoline carboxamides as dual p70S6k/Akt inhibitors for the treatment of tumors driven by alterations to the PI3K/Akt/mTOR (PAM) pathway. Through the screening of in-house proprietary kinase library, 4-benzylamino-quinazoline-8-carboxylic acid amide stood out, with sub-micromolar p70S6k biochemical activity, as the starting point for a structurally enabled p70S6K/Akt dual inhibitor program that led to the discovery of M2698, a dual p70S6k/Akt inhibitor. M2698 is kinase selective, possesses favorable physical, chemical, and DMPK profiles, is orally available and well tolerated, and displayed tumor control in multiple studies of PAM pathway-driven tumors.

PubMed: 34596404
DOI: 10.1021/acs.jmedchem.1c01087

実験手法

X-RAY DIFFRACTION (3 Å)