AM-643

AM-643 is a FLAP inhibitor with human IC₅₀ of 2 nM, oral activity, and dermal activity.AM-643 selectively inhibits FLAP, reduces leukotriene biosynthesis and reduces inflammatory ear swelling.AM-643 can be used for the research of skin disorders involving leukotriene production^[1]. In Vitro:AM-643 (compound 6) potently inhibits ³H-ligand binding to human polymorphonuclear leukocyte-derived FLAP membranes with an IC₅₀ of 2 nM^[1].
AM-643 potently inhibits calcium ionophore-induced LTB₄ synthesis in isolated human leukocytes with an IC₅₀ of 0.6 nM^[1].
AM-643 (15 min-5 h) inhibits calcium ionophore-induced LTB₄ synthesis in human whole blood with an IC₅₀ of 161 nM after 15 minutes of pre-incubation and an IC₅₀ of 81 nM after 5 hours of pre-incubation^[1].
AM-643 inhibits human CYP 3A4 with an IC₅₀ of 8.8 μM, human CYP 2C9 with an IC₅₀ of 4.5 μM, and does not inhibit human CYP 2D6 at concentrations up to 30 μM^[1]. In Vivo:AM-643 (compound 6) (30 mg/kg; p.o.; single dose) produces a 65% inhibition of arachidonic acid-induced ear edema and a 57% reduction in CysLT concentrations in mouse ear tissue^[1].
AM-643 (0.01, 0.1%; topical; single dose) produces a 61% inhibition of arachidonic acid-induced ear edema, a 37% reduction in CysLT concentrations, and a 55% reduction in LTB₄ concentrations in mouse ear tissue in vivo in a concentration-dependent manner^[1].
AM-643 (10 mg/mL; topical; single dose; occluded for 24 hours) causes no dermal irritancy and results in detectable systemic exposure in abraded healthy male rats^[1].