Discovery of Indoline-Based, Natural-Product-like Compounds as Probes of Focal Adhesion Kinase Signaling Pathways

Par Conseil national de recherches du Canada

DOI	Trouver le DOI : https://doi.org/10.1021/cc8001525
Auteur	Rechercher : Poondra, Rajamohan R.¹; Rechercher : Kumar, N. Niranjan; Rechercher : Bijian, Krikor; Rechercher : Prakesch, Michael; Rechercher : Campagna-Slater, Vale´rie; Rechercher : Reayi, Ayub¹; Rechercher : Reddy, P. Thirupathi²; Rechercher : Choudhry, Asna¹; Rechercher : Barnes, Michael L.¹; Rechercher : Leek, Donald M.¹; Rechercher : Daroszewska, Malgosia¹; Rechercher : Lougheed, Caroline; Rechercher : Xu, Bin; Rechercher : Schapira, Matthieu; Rechercher : Alaoui-Jamali, Moulay A.; Rechercher : Arya, Prabhat¹
Affiliation	Conseil national de recherches du Canada. Institut Steacie des sciences moléculaires du CNRC Conseil national de recherches du Canada. Institut national de nanotechnologie
Format	Texte, Article
Sujet	indoline-based; molecule modulators; protein; synthesis; aminoindoline-derived; compounds
Résumé	With the goal of identifying small molecule modulators of protein−protein interactions, we developed a solid-phase synthesis method, which was then successfully utilized in a library generation of 164 aminoindoline-derived, natural-product-like compounds. This library and several other related intermediates synthesized during this project were then subjected to different biological assays in search of small molecule modulators of focal adhesion kinase (FAK)-mediated signaling pathways. This study included (i) an in vitro, full length FAK inhibition assay, (ii) a cell proliferation assay, and (iii) a wound healing assay. In FAK inhibition assay, eight library members (5−12) and three aminoindoline derivatives (13, 14, and 2) were identified as promising candidates. Compounds 13 and 2 inhibited the FAK activity by 25−45% at 10 μM. These two lead compounds also showed activity in a wound healing assay. To our knowledge, these aminoindoline-derived small molecules belong to a new family of FAK inhibitors.
Date de publication	2009-03-09
Dans	Journal of Combinatorial Chemistry 11, nº 2 (9 mars 2009) : 303–309.
Langue	anglais
Publications évaluées par des pairs	Oui
Numéro NPARC	16457845
Exporter la notice	Exporter en format RIS
Signaler une correction	Signaler une correction (s'ouvre dans un nouvel onglet)
Identificateur de l’enregistrement	691a9b0f-eab7-43ac-b727-12235a463b54
Enregistrement créé	2011-02-14
Enregistrement modifié	2020-04-16

Date de modification :: 2024-06-30