Your browser doesn't support javascript.
loading
Structure-based design of novel quinoxaline-2-carboxylic acids and analogues as Pim-1 inhibitors.
Oyallon, Bruno; Brachet-Botineau, Marie; Logé, Cédric; Bonnet, Pascal; Souab, Mohamed; Robert, Thomas; Ruchaud, Sandrine; Bach, Stéphane; Berthelot, Pascal; Gouilleux, Fabrice; Viaud-Massuard, Marie-Claude; Denevault-Sabourin, Caroline.
Affiliation
  • Oyallon B; EA GICC - ERL 7001 CNRS « Groupe Innovation et Ciblage Cellulaire ¼, Team Innovation Moléculaire et Thérapeutique, University of Tours, F-37200, Tours, France.
  • Brachet-Botineau M; CNRS ERL7001 LNOx « Leukemic Niche and RedOx Metabolism ¼ - EA GICC, University of Tours, F-37000, Tours, France; CHRU de Tours, Service d'Hématologie Biologique, F-37044, Tours, France.
  • Logé C; Université de Nantes, Nantes Atlantique Universités, Département de Chimie Thérapeutique, Cibles et Médicaments des Infections et du Cancer, IICIMED- EA1155, Institut de Recherche en Santé 2, F-44200, Nantes, France.
  • Bonnet P; UMR University of Orléans-CNRS 7311, Institut de Chimie Organique et Analytique (ICOA), University of Orléans, F-45067, Orléans, France.
  • Souab M; Sorbonne Universités, USR3151 CNRS/UPMC, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique, Place Georges Teissier, F-29688, Roscoff, France.
  • Robert T; Sorbonne Universités, USR3151 CNRS/UPMC, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique, Place Georges Teissier, F-29688, Roscoff, France.
  • Ruchaud S; Sorbonne Universités, USR3151 CNRS/UPMC, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique, Place Georges Teissier, F-29688, Roscoff, France.
  • Bach S; Sorbonne Universités, USR3151 CNRS/UPMC, Plateforme de criblage KISSf (Kinase Inhibitor Specialized Screening Facility), Station Biologique, Place Georges Teissier, F-29688, Roscoff, France.
  • Berthelot P; UMR-S 1172 - JPArc - Centre de Recherche Jean-Pierre AUBERT Neurosciences et Cancer, University of Lille, Inserm, CHU Lille, F-59000, Lille, France.
  • Gouilleux F; CNRS ERL7001 LNOx « Leukemic Niche and RedOx Metabolism ¼ - EA GICC, University of Tours, F-37000, Tours, France.
  • Viaud-Massuard MC; EA GICC - ERL 7001 CNRS « Groupe Innovation et Ciblage Cellulaire ¼, Team Innovation Moléculaire et Thérapeutique, University of Tours, F-37200, Tours, France.
  • Denevault-Sabourin C; EA GICC - ERL 7001 CNRS « Groupe Innovation et Ciblage Cellulaire ¼, Team Innovation Moléculaire et Thérapeutique, University of Tours, F-37200, Tours, France. Electronic address: caroline.sabourin@univ-tours.fr.
Eur J Med Chem ; 154: 101-109, 2018 Jun 25.
Article in En | MEDLINE | ID: mdl-29778892
We identified a new series of quinoxaline-2-carboxylic acid derivatives, targeting the human proviral integration site for Moloney murine leukemia virus-1 (HsPim-1) kinase. Seventeen analogues were synthesized providing useful insight into structure-activity relationships studied. Docking studies realized in the ATP pocket of HsPim-1 are consistent with an unclassical binding mode of these inhibitors. The lead compound 1 was able to block HsPim-1 enzymatic activity at nanomolar concentrations (IC50 of 74 nM), with a good selectivity profile against a panel of mammalian protein kinases. In vitro studies on the human chronic myeloid leukemia cell line KU812 showed an antitumor activity at micromolar concentrations. As a result, compound 1 represents a promising lead for the design of novel anticancer targeted therapies.
Subject(s)
Key words

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Quinoxalines / Drug Design / Protein Kinase Inhibitors / Proto-Oncogene Proteins c-pim-1 Limits: Humans Language: En Journal: Eur J Med Chem Year: 2018 Document type: Article Affiliation country: Francia Country of publication: Francia

Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Quinoxalines / Drug Design / Protein Kinase Inhibitors / Proto-Oncogene Proteins c-pim-1 Limits: Humans Language: En Journal: Eur J Med Chem Year: 2018 Document type: Article Affiliation country: Francia Country of publication: Francia