SGC-AAK1-1: A Chemical Probe Targeting AAK1 and BMP2K

Autor(es):Mostrar menos -

Wells, Carrow ^{[1, 2]} ; Counago, Rafael M. ^{[3, 4]} ; Limas, Juanita C. ^[5] ; Almeida, Tuanny L. ^{[3, 4]} ; Cook, Jeanette Gowen ^[6] ; Drewry, David H. ^{[1, 2]} ; Elkins, Jonathan M. ^{[3, 7]} ; Gileadi, Opher ^{[3, 7]} ; Kapadia, Nirav R. ^{[1, 2]} ; Lorente-Macias, Alvaro ^[8] ; Pickett, Julie E. ^[1] ; Riemen, Alexander ^[9] ; Ruela-de-Sousa, Roberta R. ^{[3, 4]} ; Willson, Timothy M. ^{[1, 2]} ; Zhang, Cunyu ^[10] ; Zuercher, William J. ^{[1, 2, 11]} ; Zutshi, Reena ^[9] ; Axtman, Alison D. ^{[1, 2]}

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^[1] UNC CH, UNC Eshelman Sch Pharm, SGC, Chapel Hill, NC 27599 - USA

^[2] UNC CH, UNC Eshelman Sch Pharm, Div Chem Biol & Med Chem, Chapel Hill, NC 27599 - USA

^[3] Univ Estadual Campinas, UNICAMP, Inst Biol, SGC, Dept Genet & Evolucao, BR-13083886 Campinas, SP - Brazil

^[4] Univ Estadual Campinas, Ctr Biol Mol & Engn Genet, Ctr Quim Med, BR-13083875 Campinas, SP - Brazil

^[5] UNC CH, Dept Pharmacol, Chapel Hill, NC 27599 - USA

^[6] UNC CH, Dept Biochem & Biophys, Chapel Hill, NC 27599 - USA

^[7] Univ Oxford, Nuffield Dept Clin Med, SGC, Old Rd, Campus Res Bldg, Oxford OX3 7DQ - England

^[8] Univ Granada, Dept Quim Farmaceut & Organ, E-18071 Granada - Spain

^[9] Luceome Biotechnol LLC, Tucson, AZ 85719 - USA

^[10] GlaxoSmithKline, Platform Technol Sci, Collegeville, PA 19426 - USA

^[11] UNC CH, LCCC, Chapel Hill, NC 27599 - USA

• Tipo de documento: Artigo Científico
• Fonte: ACS Medicinal Chemistry Letters; v. 11, n. 3, p. 340-345, MAR 12 2020.
• Citações Web of Science: 0

Resumo

Inhibitors based on a 3-acylaminoindazole scaffold were synthesized to yield potent dual AAK1/BMP2K inhibitors. Optimization furnished a small molecule chemical probe (SGC-AAK1-1, 25) that is potent and selective for AAK1/BMP2K over other NAK family members, demonstrates narrow activity in a kinome-wide screen, and is functionally active in cells. This inhibitor represents one of the best available small molecule tools to study the functions of AAK1 and BMP2K. (AU)

• Processo FAPESP: 14/50897-0 - INCT 2014: Centro de Química Medicinal de Acesso Aberto
• Beneficiário: Katlin Brauer Massirer
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 13/50724-5 - Centro de Biologia Química de Proteínas Quinases: alavancando desenvolvimento de fármacos através de pesquisa de acesso aberto
• Beneficiário: Paulo Arruda
• Modalidade de apoio: Auxílio à Pesquisa - Parceria para Inovação Tecnológica - PITE
• Processo FAPESP: 16/17469-0 - Desenvolvimento de ensaios celulares para avaliar e quantificar as alterações fenotípicas da inibição química da Vaccinia-Related Kinase 1 (VRK1)
• Beneficiário: Roberta Regina Ruela de Sousa
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado