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LP-533401

CAS No. : 945976-43-2

MCE 站：LP-533401

产品活性：LP-533401是调节肠道内5-羟色胺产生的色氨酸羟化酶1抑制剂。

研究领域：Metabolic Enzyme/Protease

作用靶点：Tryptophan Hydroxylase

In Vitro: LP-533401 completely inhibits serotonin production in Tph1–expressing cells (RBL2H3 cells) at a dose of 1 μM.

In Vivo: Oral administration once daily for up to 6 weeks of this small molecule prevents the development of and fully rescues, in a dose-dependent manner, osteoporosis in ovariectomized rodents because of an isolated increase in bone formation. Pharmacokinetic studies in rodents show that LP-533401 level in the brain is negligible following oral administration, indicating that it is virtually unable to cross the blood-brain barrier. Mice treated repeatedly with LP-533401 (30–250 mg/kg per day) exhibit marked 5-HT content reductions in the gut, lungs, and blood, but not in the brain. After a single LP533401 dose (250 mg/kg), lung and gut 5-HT contents decrease by 50%, whereas blood 5-HT levels remain unchanged, suggesting gut and lung 5-HT synthesis. Adult, healthy mice treated with the Tph-1 inhibitor LP-533401 show 30% decrease in circulating serotonin levels, with a consequent 30% increase in osteoblast numbers. Administration of LP533401 to mice injected with EL4 cells inhibits the decrement in osteoblast numbers and trabecular bone volume, prolongs survial, and decreases leukemic infiltration.

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