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

Author(s):Show less -

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]}

Affiliation:Show less -

^[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

• Document type: Journal article
• Source: ACS Medicinal Chemistry Letters; v. 11, n. 3, p. 340-345, MAR 12 2020.
• Web of Science Citations: 0

Abstract

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)

• FAPESP's process: 14/50897-0 - INCT 2014: Open-acess Medicinal Chemistry Centre (OpenMedChem)
• Grantee: Katlin Brauer Massirer
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/50724-5 - Protein Kinase Chemical Biology Center: supporting drug development through open-access research
• Grantee: Paulo Arruda
• Support Opportunities: Research Grants - Research Partnership for Technological Innovation - PITE
• FAPESP's process: 16/17469-0 - Development of celular assays to measure and to discover the phenotypic consequences of chemical inhibition of Vaccinia-Related Kinase 1 (VRK1)
• Grantee: Roberta Regina Ruela de Sousa
• Support Opportunities: Scholarships in Brazil - Post-Doctoral