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

Autor:	Wells C; Structural Genomics Consortium (SGC), UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, North Carolina 27599, United States.; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, UNC-CH, Chapel Hill, North Carolina 27599, United States., Couñago RM; SGC, Departamento de Genética e Evolução, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-886, Brazil.; Centro de Química Medicinal, Centro de Biologia Molecular e Engenharia Genética, UNICAMP, Campinas, SP 13083-875, Brazil., Limas JC; Department of Pharmacology, UNC-CH, Chapel Hill, North Carolina 27599, United States., Almeida TL; SGC, Departamento de Genética e Evolução, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-886, Brazil.; Centro de Química Medicinal, Centro de Biologia Molecular e Engenharia Genética, UNICAMP, Campinas, SP 13083-875, Brazil., Cook JG; Department of Biochemistry and Biophysics, UNC-CH, Chapel Hill, North Carolina 27599, United States., Drewry DH; Structural Genomics Consortium (SGC), UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, North Carolina 27599, United States.; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, UNC-CH, Chapel Hill, North Carolina 27599, United States., Elkins JM; SGC, Departamento de Genética e Evolução, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-886, Brazil.; SGC, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, U.K., Gileadi O; SGC, Departamento de Genética e Evolução, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-886, Brazil.; SGC, Nuffield Department of Clinical Medicine, University of Oxford, Old Road Campus Research Building, Oxford, OX3 7DQ, U.K., Kapadia NR; Structural Genomics Consortium (SGC), UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, North Carolina 27599, United States.; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, UNC-CH, Chapel Hill, North Carolina 27599, United States., Lorente-Macias A; Departamento de Química Farmacéutica y Orgánica, University of Granada, Granada, 18071, Spain., Pickett JE; Structural Genomics Consortium (SGC), UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, North Carolina 27599, United States.; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, UNC-CH, Chapel Hill, North Carolina 27599, United States., Riemen A; Luceome Biotechnologies, LLC, Tucson, Arizona 85719, United States., Ruela-de-Sousa RR; SGC, Departamento de Genética e Evolução, Instituto de Biologia, Universidade Estadual de Campinas (UNICAMP), Campinas, SP 13083-886, Brazil.; Centro de Química Medicinal, Centro de Biologia Molecular e Engenharia Genética, UNICAMP, Campinas, SP 13083-875, Brazil., Willson TM; Structural Genomics Consortium (SGC), UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, North Carolina 27599, United States.; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, UNC-CH, Chapel Hill, North Carolina 27599, United States., Zhang C; Platform Technology Sciences, GlaxoSmithKline, Collegeville, Pennsylvania 19426, United States., Zuercher WJ; Structural Genomics Consortium (SGC), UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, North Carolina 27599, United States.; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, UNC-CH, Chapel Hill, North Carolina 27599, United States.; Lineberger Comprehensive Cancer Center (LCCC), UNC-CH, Chapel Hill, North Carolina 27599, United States., Zutshi R; Luceome Biotechnologies, LLC, Tucson, Arizona 85719, United States., Axtman AD; Structural Genomics Consortium (SGC), UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill (UNC-CH), Chapel Hill, North Carolina 27599, United States.; Division of Chemical Biology and Medicinal Chemistry, UNC Eshelman School of Pharmacy, UNC-CH, Chapel Hill, North Carolina 27599, United States.
Jazyk:	angličtina
Zdroj:	ACS medicinal chemistry letters [ACS Med Chem Lett] 2019 Oct 23; Vol. 11 (3), pp. 340-345. Date of Electronic Publication: 2019 Oct 23 (Print Publication: 2020).
DOI:	10.1021/acsmedchemlett.9b00399
Abstrakt:	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. Competing Interests: The authors declare no competing financial interest. (Copyright © 2019 American Chemical Society.)
Databáze:	MEDLINE
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