title: Recent progress in the design, study, and development of c-Jun N-terminal kinase inhibitors as anticancer agents.
abstract: The c-Jun N-terminal kinase (JNK) family, with its three members JNK1, JNK2, and JNK3, is a subfamily of mitogen-activated protein kinases. Involved in many aspects of cellular processes, JNK has been also associated with pathological states such as neurodegenerative diseases, inflammation, and cancers. In oncology, each isoform plays a distinct role depending on the context of the targeted tissue/organ, the tumor stage, and, most likely, the signaling pathway activated upstream. Consequently, the current challenge in finding new successful anti-JNK therapies is to design isoform-selective inhibitors of the JNKs. In this review, a particular focus is given to the JNK inhibitors that have been developed thus far when examining 3D structures of various JNK-inhibitor complexes. Using current data regarding structure-activity relationships and medicinal chemistry approaches, our objective is to provide a better understanding of the design and development of selective JNK inhibitors in the present and future.
authors.affiliation: OriBase Pharma, Cap Gamma, Parc Euromédecine, 34090 Montpellier, France; Laboratoire de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Université Mohammed V-Agdal, Faculté des Sciences, B.P. 1014 Rabat, Morocco.
authors.forename: Abdellah
authors.initials: A
authors.lastname: Messoussi
authors.affiliation: OriBase Pharma, Cap Gamma, Parc Euromédecine, 34090 Montpellier, France.
authors.forename: Clémence
authors.initials: C
authors.lastname: Feneyrolles
authors.affiliation: OriBase Pharma, Cap Gamma, Parc Euromédecine, 34090 Montpellier, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Bros
authors.affiliation: OriBase Pharma, Cap Gamma, Parc Euromédecine, 34090 Montpellier, France.
authors.forename: Arthur
authors.initials: A
authors.lastname: Deroide
authors.affiliation: OriBase Pharma, Cap Gamma, Parc Euromédecine, 34090 Montpellier, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Daydé-Cazals
authors.affiliation: OriBase Pharma, Cap Gamma, Parc Euromédecine, 34090 Montpellier, France.
authors.forename: Gwénaël
authors.initials: G
authors.lastname: Chevé
authors.affiliation: OriBase Pharma, Cap Gamma, Parc Euromédecine, 34090 Montpellier, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Van Hijfte
authors.affiliation: OriBase Pharma, Cap Gamma, Parc Euromédecine, 34090 Montpellier, France.
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Fauvel
authors.affiliation: Laboratoire de Chimie des Plantes et de Synthèse Organique et Bioorganique, URAC23, Université Mohammed V-Agdal, Faculté des Sciences, B.P. 1014 Rabat, Morocco.
authors.forename: Khalid
authors.initials: K
authors.lastname: Bougrin
authors.affiliation: OriBase Pharma, Cap Gamma, Parc Euromédecine, 34090 Montpellier, France. Electronic address: ayasri@oribase-pharma.com.
authors.forename: Aziz
authors.initials: A
authors.lastname: Yasri
mesh_terms: D000255:Adenosine Triphosphate / Q000737:chemistry / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000627:therapeutic use; D001667:Binding, Competitive; D015195:Drug Design; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy; D020033:Protein Isoforms / Q000037:antagonists & inhibitors / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000737:chemistry* / Q000627:therapeutic use; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors; D000255:Adenosine Triphosphate; D048031:JNK Mitogen-Activated Protein Kinases