GAL-021 an intravenous BKCa-channel blocker.

Using inside-out patches in GH3 cells, GAL-021 concentration-dependently inhibits single-channel KCa1.1 activity. When evaluated against 12 different cardiac ion channels, inhibition is 35% or less at 30 μM. No significant kinase inhibition is observed at 10 μM. At 30 μM in the radioligand binding assays, interactions (defined as >50% radioligand displacement) are detected at adenosine A1 (65% I), A2A (79% I, IC50: 5 μM), and A3 (93% I; IC50: 1 μM) receptors, at 5-HT2B receptors (60% I; IC50: 30 μM).

GAL-021 administered intravenously (i.v.) mitigates opiate-induced respiratory depression in both rats and nonhuman primates, preserving morphine's analgesic effects in rats. Furthermore, its capacity to stimulate ventilation in rats is diminished following carotid sinus nerve transection. This ventilatory stimulation by GAL-021 is also reduced in mice devoid of the pore-forming α-subunit of the KCa 1.1 channel.

GAL-021 is dissolved in DMSO, and final assay concentration of DMSO is 0.1% or less. The effects of GAL-021 (30 μM) on a panel of 55 receptors, transporters, and ion channels are evaluated using radioligand binding analyses. Potential kinase inhibition by GAL-021 (10 μM) is assessed using the Kinase HotSpot Screen where activity of 50 kinases is measured in the presence of adenosine triphosphate (10 μM)[1].