Azalanstat (dihydrochloride)

Azalanstat dihydrochloride (RS-21607 dihydrochloride) is an inhibitor of heme oxygenase and lanosterol 14α-demethylase, with inhibitory activity against HO-1 (IC₅₀ = 5.5 µM) and HO-2 (IC₅₀ = 24.5 µM). Azalanstat dihydrochloride reduces the maturation rate of rat oocytes, increases rat oocyte degeneration, and partially inhibits progesterone production in preovulatory follicles of rats^[1][2][3]. In Vitro:Azalanstat dihydrochloride (Compound I) inhibits rat spleen microsomal HO-1 (IC₅₀ = 5.8 μM) and rat brain microsomal HO-2 (IC₅₀ = 28.0 μM) in vitro, with a selectivity index of 5 for HO-1 over HO-2^[1].
Azalanstat dihydrochloride (0-100 μM) inhibits the activity of rat liver microsomal CYP3A1/3A2 in vitro, with an IC₅₀ of 48.1 μM^[1].
Azalanstat dihydrochloride (0-200 μM; 3-24 h, or 6 h + 24 h inhibitor-free culture) reduces GVBD in a dose- and time-dependent manner at high concentrations (≥50 μM for 6 h treatment, ≥10 μM for 24 h treatment), while increasing the degree of oocyte degeneration; notably, oocyte degeneration becomes irreversible after 6 h of treatment at 100 μM^[2].
Azalanstat dihydrochloride (1-100 μM; 6-24 h with 5 μg/mL LH) reduces LH-induced GVBD in a dose-dependent manner, accompanied by increased degeneration of oocytes and follicles at 1-100 μM with a 24 h treatment^[2].
Azalanstat dihydrochloride (1-100 μM; 6-24 h with 5 μg/mL LH) partially inhibits LH-induced progesterone synthesis in preovulatory rat follicles in vitro in a dose-dependent manner when applied at concentrations of 1, 50, and 100 μM for 6 or 24 h^[2]. In Vivo:Azalanstat (2.15-215 μg/bursa; intracapsular injection; single administration) significantly inhibits ovulation in immature female Wistar rats at the highest tested intracapsular dose^[2].