Tryptophan hydroxylase 1 (Tph1) is the initial enzyme in the biosynthesis of gut-derived serotonin. LP-533401 HCl inhibits human Tph1 in vitro with an IC50 value of 0.7 μM. It also blocked the activity of purified recombinant human Tph2 with similar potency. In rat mastocytoma RBL2H3 cells that endogenously express Tph1, LP-533401 inhibited serotonin production with an IC50 value of 0.4 μM[2]. The complete inhibition on serotonin production in Tph1-expressing cells was found at the concentration of 1 μM[3]. In ovariectomized female C57Bl6/J mice, administration of LP-533401 (10 – 250 mg/kg/day) for 28 days significantly increased the bone mass, as well as the bone formation parameters, such as osteoblast numbers, bone formation rate, and osteocalcin serum levels when compared to vehicle-treated controls. LP-533401 treatment also dose-dependently decreased the level of serotonin in serum, whereas the brain serotonin content remained unaltered[3].
作用机制
LP-533401 HCl inhibits Tph1 activity by interacting with the two amino acids, Tyr235 and Phe241, near Tph1 catalytic site.
搜索
