4D0W

Pyrrole-3-carboxamides as potent and selective JAK2 inhibitors

4D0W の概要

• エントリーDOI: 10.2210/pdb4d0w/pdb
• 関連するPDBエントリー: 4D0X 4D1S
• 分子名称: TYROSINE-PROTEIN KINASE JAK2, GLYCEROL, 5-(2-aminopyrimidin-4-yl)-2-(5-chloro-2-methylphenyl)-1H-pyrrole-3-carboxamide, ... (4 entities in total)
• 機能のキーワード: transferase, drug discovery, protein kinase inhibitors, structure-activity relationship, polycythemia vera, tumour cell proliferation inhibition, anti-cancer agents
• 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: 35617.85

構造登録者

Bertrand, J.,Canevari, G.,Fasolini, M.,Brasca, M.G.,Nesi, M.,Avanzi, N.,Ballinari, D.,Bandiera, T.,Bindi, S.,Carenzi, D.,Casero, D.,Ceriani, L.,Ciomei, M.,Cirla, A.,Colombo, M.,Cribioli, S.,Cristiani, C.,Della Vedova, F.,Fachin, G.,Felder, E.R.,Galvani, A.,Isacchi, A.,Mirizzi, D.,Motto, I.,Panzeri, A.,Pesenti, E.,Vianello, P.,Gnocchi, P.,Donati, D. (登録日: 2014-04-30, 公開日: 2014-07-23, 最終更新日: 2024-10-23)

主引用文献

Brasca, M.G.,Nesi, M.,Avanzi, N.,Ballinari, D.,Bandiera, T.,Bertrand, J.,Bindi, S.,Canevari, G.,Carenzi, D.,Casero, D.,Ceriani, L.,Ciomei, M.,Cirla, A.,Colombo, M.,Cribioli, S.,Cristiani, C.,Della Vedova, F.,Fachin, G.,Fasolini, M.,Felder, E.R.,Galvani, A.,Isacchi, A.,Mirizzi, D.,Motto, I.,Panzeri, A.,Pesenti, E.,Vianello, P.,Gnocchi, P.,Donati, D.
Pyrrole-3-Carboxamides as Potent and Selective Jak2 Inhibitors.
Bioorg.Med.Chem., 22:4998-, 2014

PubMed Abstract: We report herein the discovery, structure guided design, synthesis and biological evaluation of a novel class of JAK2 inhibitors. Optimization of the series led to the identification of the potent and orally bioavailable JAK2 inhibitor 28 (NMS-P953). Compound 28 displayed significant tumour growth inhibition in SET-2 xenograft tumour model, with a mechanism of action confirmed in vivo by typical modulation of known biomarkers, and with a favourable pharmacokinetic and safety profile.

PubMed: 25009002
DOI: 10.1016/J.BMC.2014.06.025

実験手法

X-RAY DIFFRACTION (1.77 Å)