LP-533401 is a Tryptophan hydroxylase 1 inhibitor that regulates serotonin production in the gut. LP-533401 completely inhibits serotonin production in Tph1–expressing cells (RBL2H3 cells) at a dose of 1 μM[1].
体内研究
When administered orally daily for up to 6 weeks, LP-533401 dose-dependently prevents and reverses osteoporosis in ovariectomized rodents by selectively increasing bone formation, without significant absorption into the brain, as indicated by its negligible brain levels and inability to cross the blood-brain barrier in pharmacokinetic studies[1].
Repeated treatment with LP-533401 results in significant reductions in 5-HT content in the gut, lungs, and blood of mice, without affecting brain 5-HT levels, which underscores its effect on serotonin synthesis outside the central nervous system[2].
In healthy adult mice, treatment with LP-533401 leads to a 30% decrease in circulating serotonin levels and a consequent 30% increase in osteoblast numbers. Furthermore, in mice injected with EL4 cells, LP-533401 treatment inhibits reductions in osteoblast numbers and trabecular bone volume, prolongs survival, and diminishes leukemic infiltration, showcasing its potential in bone health and leukemia intervention[3].
体外研究
LP-533401 is a Tryptophan hydroxylase 1 inhibitor that regulates serotonin production in the gut. LP-533401 completely inhibits serotonin production in Tph1–expressing cells (RBL2H3 cells) at a dose of 1 μM[1].
作用机制
LP-533401 interacts with two amino acids, Tyr235 and Phe241, near Tph1 catalytic site. [2]
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