Halofantrine (hydrochloride)

Halofantrine hydrochloride (SKF-102886 hydrochloride; WR-171669 hydrochloride) is a blocker that delays the delayed rectifier potassium current by inhibiting human ERG channels, and it is a potent antimalarial agent. Halofantrine hydrochloride inhibits the Cap1-dependent oxidative stress response of Candida albicans, suppresses ROS responses, and enhances the antifungal (Fungal) activity of oxidative damage agents. Halofantrine hydrochloride exhibits antifungal activity in the Galleria mellonella model, and shows antimalarial activity against Plasmodium strains both in vitro and in animal models. Halofantrine hydrochloride can be used in studies related to invasive candidiasis, falciparum malaria, and vivax malaria^[1][2]. IC50 & Target:Malaria^[1]. HERG channel^[2]. In Vitro:Halofantrine hydrochloride (24-48 h) acts synergistically with oxidative damage agents Plumbagin (HY-N1497), menadione, and H₂O₂ against Candida albicans strains SC5314 and SN152, with FICI values of 0.0938, 0.1563, and 0.2526, respectively^[1].
The combination of halofantrine hydrochloride (24 h) and H₂O₂ retains synergistic activity against Candida albicans hog1Δ/Δ and rad53Δ/Δ strains (with FICI values of 0.5 and 0.2813, respectively), but shows no synergistic activity against cap1Δ/Δ, ybp1Δ/Δ or gpx3Δ/Δ strains when combined with H₂O₂, indicating that its oxidative stress inhibitory effect depends on the Cap1-Ybp1 pathway^[1].
Halofantrine inhibits chloroquine (HY-17589A)-sensitive Plasmodium falciparum in vitro, with an IC₅₀ value of 1.5-2.5 μg/L^[2].
Halofantrine (1.3-3.9 μg/L) inhibits chloroquine-resistant Plasmodium falciparum in vitro, with an IC₅₀ value of 1.3-3.9 μg/L^[2].
Halofantrine (10 μmol/L) inhibits glucose-dependent proton efflux in Plasmodium berghei-infected mouse erythrocytes at a concentration of 10 μmol/L in vitro^[2].
Halofantrine inhibits Plasmodium falciparum in vitro, with an ID₅₀ of 4.0 μg/L^[2]. In Vivo:Halofantrine hydrochloride (0-2 mg/kg; injection; single dose) reduces the mortality rate of Galleria mellonella larvae infected with Candida albicans to 40% during an 8-day observation period^[1].
Halofantrine (10-640 mg/kg; s.c.; p.o.; daily; single dose) exhibits potent in vivo antimalarial activity in mice infected with Plasmodium berghei, but shows poor oral bioavailability at doses up to 640 mg/kg^[2].
Halofantrine (35-140 mg/kg; p.o.; 7-day regimen; single dose) alleviates Plasmodium falciparum infection in Aotus monkeys^[2].