他拉罗唑

IC50: 0.46/5.1 nM (CYP26B1/A1)

When HepG2 cells are cotreated with atRA and Talarozole (1 μM), 4-OH-RA and 4-oxo-RA formation is significantly decreased.

A maximum 84% inhibition of CYP26 activity at 0.5 hours post-dose is predicted based on Talarozole (TLZ) C _max of 80 nM and a K _i of 1 nM following a single dose of Talarozole. Due to the short Talarozole half-life (2.2 hrs) CYP26 activity is predicted to return to 100% by 12 hours. In agreement with the predictions, at RA concentrations are increased by 82, 63 and 60% at 4 hours post-dose in the serum, liver and testes, respectively, and concentrations returned to baseline by 24 hours. Following multiple doses of Talarozole, liver CYP26 mRNA and activity are increased suggesting autoinduction of CYP26 due to increased at RA concentrations. In agreement, at RA concentrations are elevated in serum and liver at all timepoints measured. This increase in at RA concentrations is associated with increased mRNA of the mitochondrial biogenesis markers PGC-1β and NRF-1 in comparison to control mice.