A chemical probe targeting AAK1 and BMP2K

DOI: 10.1021/acsmedchemlett.9b00399

Authors: Carrow Wells (Structural Genomics Consortium (SGC), University of North Carolina at Chapel Hill (UNC-CH)) , Rafael M. Counago (SGC, Universidade Estadual de Campinas (UNICAMP)) , Juanita C. Limas (University of North Carolina at Chapel Hill (UNC-CH)) , Tuanny L. Almeida (SGC, Universidade Estadual de Campinas (UNICAMP)) , Jeanette Gowen Cook (University of North Carolina at Chapel Hill (UNC-CH)) , David H Drewry (Structural Genomics Consortium (SGC), University of North Carolina at Chapel Hill (UNC-CH)) , Jonathan M. Elkins (SGC, Universidade Estadual de Campinas (UNICAMP); SGC, University of Oxford) , Opher Gileadi (SGC, Universidade Estadual de Campinas (UNICAMP); SGC, University of Oxford) , Nirav R. Kapadia (Structural Genomics Consortium (SGC), University of North Carolina at Chapel Hill (UNC-CH)) , Alvaro Lorente-Macias (University of Granada) , Julie E. Pickett (Structural Genomics Consortium (SGC), University of North Carolina at Chapel Hill (UNC-CH)) , Alexander Riemen (Luceome Biotechnologies) , Roberta R. Ruela-De-Sousa (SGC, Universidade Estadual de Campinas (UNICAMP)) , Timothy M. Willson (Structural Genomics Consortium (SGC), University of North Carolina at Chapel Hill (UNC-CH)) , Cunyu Zhang (GlaxoSmithKline) , William J Zuercher (Structural Genomics Consortium (SGC), University of North Carolina at Chapel Hill (UNC-CH)) , Reena Zutshi (Luceome Biotechnologies) , Alison D. Axtman (Structural Genomics Consortium (SGC), University of North Carolina at Chapel Hill (UNC-CH))
Co-authored by industrial partner: Yes

Type: Journal Paper
Journal: Acs Medicinal Chemistry Letters

State: Published (Approved)
Published: October 2019
Diamond Proposal Number(s): 14664

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.

Journal Keywords: AAK1; BMP2K; acylaminoindazole; NAK family; endocytosis; protein kinase

Subject Areas: Chemistry, Biology and Bio-materials


Instruments: I03-Macromolecular Crystallography

Added On: 28/10/2019 12:15

Discipline Tags:

Health & Wellbeing Biochemistry Chemistry Structural biology Organic Chemistry Drug Discovery Life Sciences & Biotech

Technical Tags:

Diffraction Macromolecular Crystallography (MX)