5AEP

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

Summary for 5AEP

• Entry DOI: 10.2210/pdb5aep/pdb
• Descriptor: 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)
• Functional Keywords: transferase, protein kinase, jak2, myeloproliferative disorders, tumour cell proliferation inhibition, anti-cancer agents
• Biological source: HOMO SAPIENS (HUMAN)
• Total number of polymer chains: 1
• Total formula weight: 35549.78

Authors

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. (deposition date: 2015-01-08, release date: 2015-04-29, Last modification date: 2024-01-10)

Primary citation

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

Experimental method

X-RAY DIFFRACTION (1.95 Å)