LP-533401

An inhibitor of gut-derived serotonin biosynthesis

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库存: 现货

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1mg

￥612.00

490.00

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5mg

￥1225.00

980.00

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10mg

￥1850.00

1480.00

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25mg

￥3450.00

2760.00

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货号: ajci72408
CAS: 945976-43-2
别名: L-苯丙氨酸,4[2-AMINO-6-(3-[2,2,2-三氟-1-氟[1,1'-联苯-4-乙氧基])]-4-PYRIMIDINYL]—
分子式: C27H22F4N4O3
分子量: 526.5
纯度: >98%
溶解度: DMF: 10 mg/ml,DMF:PBS(pH7.2) (1:2): 0.33 mg/ml,DMSO: 5 mg/ml
储存: Store at -20°C
库存: 现货

Background

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].

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[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 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[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 LP533401 to mice injected with EL4 cells inhibits the decrement in osteoblast numbers and trabecular bone volume, prolongs survial, and decreases leukemic infiltration[3].

参考文献:
[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.

Protocol

Animal experiment:

Mice: 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].

参考文献:

[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.