BMT-090605 is a potent, selective AAK1 inhibitor, with an IC50 of 0.6 nM. BMT-090605 shows antinociceptive activity. BMT-090605 inhibits BMP-2-inducible protein kinase (BIKE) and Cyclin G-associated kinase (GAK) with IC50s of 45 and 60 nM, respectively[1].
BMT-090605 shows a cellular IC50 of 0.63 ±0.39 nM for AAK1[1].
BMT-090605 (0.3-3 µg/rat; intrathecally at lumbar level L5/L6) causes antinociception by inhibiting AAK1 in the spinal cord[1].The high dose of BMT-090605 (3 µg/rat) showed efficacy comparable to intrathecal clonidine (3 µg/rat). Exposure measurements from this study indicated that brain and plasma levels of BMT-090605 were <4 nM, whereas measurable levels (90-317 nM) were observed in lumbar spinal cord[1].
[1]. Kostich W, et al. Inhibition of AAK1 Kinase as a Novel Therapeutic Approach to Treat Neuropathic Pain. J Pharmacol Exp Ther. 2016 Sep;358(3):371-86.