1. Academic Validation
  2. Pyrrole-3-carboxamides as potent and selective JAK2 inhibitors

Pyrrole-3-carboxamides as potent and selective JAK2 inhibitors

  • Bioorg Med Chem. 2014 Sep 1;22(17):4998-5012. doi: 10.1016/j.bmc.2014.06.025.
Maria Gabriella Brasca 1 Marcella Nesi 2 Nilla Avanzi 2 Dario Ballinari 2 Tiziano Bandiera 2 Jay Bertrand 2 Simona Bindi 2 Giulia Canevari 2 Davide Carenzi 2 Daniele Casero 2 Lucio Ceriani 2 Marina Ciomei 2 Alessandra Cirla 2 Maristella Colombo 2 Sabrina Cribioli 2 Cinzia Cristiani 2 Franco Della Vedova 2 Gabriele Fachin 2 Marina Fasolini 2 Eduard R Felder 2 Arturo Galvani 2 Antonella Isacchi 2 Danilo Mirizzi 2 Ilaria Motto 2 Achille Panzeri 2 Enrico Pesenti 2 Paola Vianello 2 Paola Gnocchi 2 Daniele Donati 2
Affiliations

Affiliations

  • 1 Nerviano Medical Sciences S.r.l., Oncology, Viale Pasteur 10, 20014 Nerviano (MI), Italy. Electronic address: gabriella.brasca@nervianoms.com.
  • 2 Nerviano Medical Sciences S.r.l., Oncology, Viale Pasteur 10, 20014 Nerviano (MI), Italy.
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.

Keywords

Anti-cancer agents; JAK2; Myeloproliferative disorders; Protein kinase inhibitor; Tumour cell proliferation inhibition.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-129679
    JAK2 Inhibitor
    JAK