New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Journal Articles Molecules Year : 2021

New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation

Noël Pinaud

Abstract

Proviral integration site for Moloney murine leukemia virus (Pim)-1/2 kinase overexpression has been identified in a variety of hematologic (e.g., multiple myeloma or acute myeloid leukemia (AML)) and solid (e.g., colorectal carcinoma) tumors, playing a key role in cancer progression, metastasis, and drug resistance, and is linked to poor prognosis. These kinases are thus considered interesting targets in oncology. We report herein the design, synthesis, structure–activity relationships (SAR) and in vitro evaluations of new quinoxaline derivatives, acting as dual Pim1/2 inhibitors. Two lead compounds (5c and 5e) were then identified, as potent submicromolar Pim-1 and Pim-2 inhibitors. These molecules were also able to inhibit the growth of the two human cell lines, MV4-11 (AML) and HCT-116 (colorectal carcinoma), expressing high endogenous levels of Pim-1/2 kinases.
Fichier principal
Vignette du fichier
molecules-26-00867-v2-1.pdf (2.4 Mo) Télécharger le fichier
Origin : Publisher files allowed on an open archive

Dates and versions

inserm-03272339 , version 1 (28-06-2021)

Identifiers

Cite

Bruno Oyallon, Marie Brachet-Botineau, Cédric Logé, Thomas Robert, Stéphane Bach, et al.. New Quinoxaline Derivatives as Dual Pim-1/2 Kinase Inhibitors: Design, Synthesis and Biological Evaluation. Molecules, 2021, 26 (4), pp.867. ⟨10.3390/molecules26040867⟩. ⟨inserm-03272339⟩
170 View
138 Download

Altmetric

Share

Gmail Facebook X LinkedIn More