title: Rational Design, Synthesis, and Biological Evaluation of 7-Azaindole Derivatives as Potent Focused Multi-Targeted Kinase Inhibitors.
abstract: Efforts were made to improve a series of potent dual ABL/SRC inhibitors based on a 7-azaindole core with the aim of developing compounds that demonstrate a wider activity on selected oncogenic kinases. Multi-targeted kinase inhibitors (MTKIs) were then derived, focusing on kinases involved in both angiogenesis and tumorigenesis processes. Antiproliferative activity studies using different cellular models led to the discovery of a lead candidate (6z) that combined both antiangiogenic and antitumoral effects. The activity of 6z was assessed against a panel of kinases and cell lines including solid cancers and leukemia cell models to explore its potential therapeutic applications. With its potency and selectivity for oncogenic kinases, 6z was revealed to be a focused MTKI that should have a bright future in fighting a wide range of cancers.
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Daydé-Cazals
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Fauvel
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Singer
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Feneyrolles
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Bestgen
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Gassiot
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Aurélia
authors.initials: A
authors.lastname: Spenlinhauer
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Warnault
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Van Hijfte
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Nozha
authors.initials: N
authors.lastname: Borjini
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Gwénaël
authors.initials: G
authors.lastname: Chevé
authors.affiliation: OriBase Pharma , Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, Montpellier 34189 CEDEX 4, France.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Yasri
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D015195:Drug Design; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007211:Indoles / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018408:Patch-Clamp Techniques; D047428:Protein Kinase Inhibitors / Q000097:blood / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: C023422:7-azaindole dimer; D007211:Indoles; D047428:Protein Kinase Inhibitors