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, <b>25</b>) 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.
ACS medicinal chemistry letters
340 - 345
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.