LK-2 is an antagonist for ASIC1a with a K d of 1.9 μM. LK-2 reduces glutamate-induced ASIC1a current-enhancement with an IC 50 of 6.6 μM. LK-2 exhibits neuroprotective efficacy in mouse ischemic stroke model, with improved motor and coordination skills. LK-2 is blood-brain barrier (BBB) penetrable.