A Chemical Probe Targeting AAK1 and BMP2K
Wells C., Counago R., Limas J., Almeida T., Cook J., Drewry D., Elkins J., Gileadi O., Kapadia N., Lorente-Macías Á., Pickett J., Riemen A., R. Ruela-de-Sousa R., Willson T., Zhang C., Zuercher W., Zutshi R., Axtman A.
<p>Inhibitors based on a 3-acylaminoindazole scaffold were synthesized to yield potent dual AAK1/BMP2K inhibitors. Optimization of this 3-acylaminoindazole scaffold 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.</p>