TES-991

TES-991 is a potent and selective human α?Amino-β-carboxymuconate-ε-semialdehyde Decarboxylase (ACMSD) inhibitor, with an IC₅₀ of 3 nM. IC50 & Target: IC50: 3 nM (hACMSD)^[1]. In Vitro: TES-991 (compounds 21) is able to significantly increase intracellular NAD⁺ levels, providing further proof of their mechanism of action. TES-991 shows an inhibition of cytochrome P450 2C19, suggesting a possible involvement of the 2H-tetrazole motif in this interaction^[1]. In Vivo: After the intravenous administration of 0.5 mg/kg, TES-991 (compound 21) shows low blood clearance, with low volumes of distribution and halflives (t_1/2) of about 4.0 and 5.0 h, respectively, although after oral administration at 5 mg/kg, the blood concentrations of TES-991 is quantifiable for up to 8 h. A moderate systemic exposure is observed for the 2H-tetrazole analogue, TES-991, a good systemic exposure is recorded for the free acid^[1].