Microglial KCa3.1 Channels as a Potential Therapeutic Target for Alzheimer’s Disease

Table 1

Structure	Pharmacokinetics/pharmacodynamics/safety	Development status
	Clotrimazole; (1) KCa3.1 IC50 70–250 nM; (2) Acute inhibition and chronic induction of cytochrome P450-dependent enzymes; (3)Liver toxic	Topical antifungal generally regarded as too toxic for internal use
	TRAM-34; (1) KCa3.1 IC50 20 nM; (2) No toxicity in 28-day and 6-month tox studies in rodents; (3) 𝑡1/2 = 2 hours (rats, primates); (4) Cbrain/Cplasma1.2; (5) Not orally available	Patented by the University of California WO 01/49663 (2001)
	ICA-17043 (senicapoc); (1) KCa3.1 IC50 11 nM; (2) Orally available in humans; (3) 𝑡1/2 = 12.8 days (humans); (4) IND enabling preclinical toxicity studies in two species	Failed to reduce number of sickling crisis in Phase-3 clinical trial for sickle cell anemia after having been found safe and effective in Phase-1 and Phase-2 Developed at Icagen
	Cyclohexadiene lactone; (1) KCa3.1 IC50 8 nM; (2) Cbrain/Cplasma10; (3) Used for traumatic brain injury studies [13]	Compounds seem to have been abandoned when Bayer pulled out of stroke research; Patented by Bayer AG Germany, DE-9619612645 (1997)