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| Cas No.: | 1040526-12-2 |
| SMILES: | C1=CC(=CC(=C1)F)C2=CC=C(C=C2)C(C(F)(F)F)OC3=NC(=NC(=C3)C4=CC=C(C=C4)C[C@@H](C(=O)O)N)N.Cl |
| Formula: | C27H23ClF4N4O3 |
| M.Wt: | 562.94 |
| Purity: | >98% |
| Sotrage: | 2 years -20°C Powder, 2 weeks 4°C in DMSO, 6 months -80°C in DMSO |
| Description: | LP-533401 hydrochloride is a tryptophan hydroxylase 1 inhibitor that regulates serotonin production in the gut. |
| Target: | Tryptophan hydroxylase 1[1] |
| In Vivo: | Oral administration once daily for up to 6 weeks of LP-533401 (25, 100 or 250 mg/kg) dose-dependently prevents the development of and fully rescues, 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[1]. 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 LP-533401 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[2]. 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 LP-533401 to mice injected with EL4 cells inhibits the decrement in osteoblast numbers and trabecular bone volume, prolongs survial, and decreases leukemic infiltration[3]. |
| In Vitro: | LP-533401 hydrochloride is a tryptophan hydroxylase 1 inhibitor. LP-533401 (1 μM) completely inhibits serotonin production in Tph1-expressing cells (RBL2H3 cells) after treatment for 3 days[1]. |
| Animal Administration: | Mice[1] Mice are treated from day 1 post-ovariectomy for 4 weeks with LP-533401 (1, 10, 100 or 250 mg per kg body weight per day) or vehicle. Next mice are treated for 4 weeks starting 2 weeks post-ovariectomy with LP-533401 (250 mg per kg body weight per day) or vehicle. lastly, mice are treated for 6 weeks starting 6 weeks post-ovariectomy with LP-533401 (25, 100 or 250 mg per kg body weight per day) or vehicle[1]. |
| References: | [1]. Yadav, V.K., et al. Inhibition of gut-derived serotonin synthesis: A potential bone anabolic treatment. Nat. Med. 16(3), 308-312 (2010). [2]. Abid S, et al. Inhibition of gut- and lung-derived serotonin attenuates pulmonary hypertension in mice. Am J Physiol Lung Cell Mol Physiol. 2012 Sep 15;303(6):L500-8. [3]. Krevvata M, et al. Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts. Blood. 2014 Oct 30;124(18):2834-46. |