5AEP

Novel pyrrole carboxamide inhibitors of JAK2 as potential treatment of myeloproliferative disorders

5AEP の概要

• エントリーDOI: 10.2210/pdb5aep/pdb
• 分子名称: TYROSINE-PROTEIN KINASE JAK2, 1-(5-chloro-2-methylphenyl)-4-(pyrrolo[2,1-f][1,2,4]triazin-4-yl)-1H-pyrrole-2-carboxamide (3 entities in total)
• 機能のキーワード: transferase, protein kinase, jak2, myeloproliferative disorders, 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: 35549.78

構造登録者

Canevari, G.,Bertrand, J.,Brasca, M.G.,Nesi, M.,Amboldi, N.,Avanzi, N.,Bindi, S.,Casero, D.,Ciomei, M.,Colombo, N.,Cribioli, S.,Fachin, G.,Felder, E.R.,Galvani, A.,Isacchi, A.,Motto, I.,Panzeri, A.,Gnocchi, P.,Donati, D. (登録日: 2015-01-08, 公開日: 2015-04-29, 最終更新日: 2024-11-20)

主引用文献

Brasca, M.G.,Gnocchi, P.,Nesi, M.,Amboldi, N.,Avanzi, N.,Bertrand, J.,Bindi, S.,Canevari, G.,Casero, D.,Ciomei, M.,Colombo, N.,Cribioli, S.,Fachin, G.,Felder, E.R.,Galvani, A.,Isacchi, A.,Motto, I.,Panzeri, A.,Donati, D.
Novel Pyrrole Carboxamide Inhibitors of Jak2 as Potential Treatment of Myeloproliferative Disorders.
Bioorg.Med.Chem., 23:2387-, 2015

PubMed Abstract: Compound 1, a hit from the screening of our chemical collection displaying activity against JAK2, was deconstructed for SAR analysis into three regions, which were explored. A series of compounds was synthesized leading to the identification of the potent and orally bioavailable JAK2 inhibitor 16 (NMS-P830), which showed an encouraging tumour growth inhibition in SET-2 xenograft tumour model, with evidence for JAK2 pathway suppression demonstrated by in vivo pharmacodynamic effects.

PubMed: 25882525
DOI: 10.1016/J.BMC.2015.03.059

実験手法

X-RAY DIFFRACTION (1.95 Å)