XE991 2HCl is a potent and selective blocker of KV7 (KCNQ) voltage-gated potassium channels which blocks KV7.2+7.3 (KCNQ2+3) / M-currents (IC50 = 0.6 - 0.98 μM) and KV7.1 (KCNQ1) homomeric channels (IC50 = 0.75 μM) but is less potent against KV7.1/minK channels (IC50 = 11.1 μM).
XE 991 2HCl (dihydrochloride), a Kv7 (KCNQ) channels blocker, potently inhibits Kv7.1 (KCNQ1), Kv7.2 (KCNQ2), Kv7.2 + Kv7.3 (KCNQ3) channel, and M-current with IC50s of 0.75 µM, 0.71 µM, 0.6 μM, and 0.98 µM, respectively[3]. XE991 and DMP 543 may prove to be superior to linopirdine as Alzheimer's disease therapeutics. Although linopirdine possesses an EC50 of 4.2 microM for enhancement of [3H]ACh release from rat brain slices, XE991 and DMP 543 have EC50S of 490 and 700 nM, respectively. Although 5 mg/kg (p.o.) linopirdine does not lead to statistically significant increases in hippocampal extracellular acetylcholine levels, 5 mg/kg (p.o.) XE991 leads to increases (maximal effect > 90% over baseline) which are sustained for 60 min[4]. XE991 at 30 μM reduced the anti-contractile response of PVAT, but had no effects on vasocontraction induced by phenylephrine (PE) in the absence of PVAT (perivascular adipose tissue). 30 μM XE991 did not affect BKCa currents in VSMCs[5].
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