title: Discovering novel 7-azaindole-based series as potent AXL kinase inhibitors.
abstract: AXL is a receptor tyrosine kinase that plays a key role in tumor growth and proliferation. The scientific community has validated AXL as therapeutic target in the treatment of cancers for several years now, and several AXL inhibitors have been developed but none of them are approved. In this context, we started to design new kinase inhibitors targeting AXL from the 7-azaindole scaffold well known to interact with the ATP binding site of the kinase. Focused screening and chemical diversification around 7-azaindole scaffold were developed, based on modeling studies and medicinal chemistry rational, leading to the discovery of a new family of hits with potent inhibitory activity against AXL.
authors.affiliation: OriBase Pharma, Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, 34189 Montpellier 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, 34189 Montpellier Cedex 4, France.
authors.forename: Léa
authors.initials: L
authors.lastname: Guiet
authors.affiliation: OriBase Pharma, Cap Gamma, Parc Euromédecine, 1682 rue de la Valsière, CS 17383, 34189 Montpellier 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, 34189 Montpellier 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, 34189 Montpellier 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, 34189 Montpellier 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, 34189 Montpellier 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, 34189 Montpellier Cedex 4, France. Electronic address: ayasri@oribase-pharma.com.
authors.forename: Abdelaziz
authors.initials: A
authors.lastname: Yasri
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D004353:Drug Evaluation, Preclinical; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D007211:Indoles / Q000737:chemistry*; D020128:Inhibitory Concentration 50; D062105:Molecular Docking Simulation; D011485:Protein Binding; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: C023422:7-azaindole dimer; D007211:Indoles; D047428:Protein Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D000255:Adenosine Triphosphate; D020794:Receptor Protein-Tyrosine Kinases; D000094963:Axl Receptor Tyrosine Kinase; C000722289:AXL protein, human
keywords: 7-Azaindole; AXL; Kinase inhibitor; Medicinal chemistry; Modeling study; Receptor tyrosine kinase