1040526-12-2

1040526-12-2 structure

Name: LP533401 HCI
Chemical Name: L-Phenylalanine, 4-[2-amino-6-[2,2,2-trifluoro-1-(3'-fluoro[1,1'-biphenyl]-4-yl)ethoxy]-4-pyrimidinyl]-, hydrochloride (1:1)
CAS Number: 1040526-12-2
Molecular Formula: C₂₇H₂₃ClF₄N₄O₃
Molecular Weight: 562.943
Catalog: Signaling Pathways Metabolic Enzyme/Protease Tryptophan Hydroxylase
Create Date: 2017-05-07 09:58:30
Modify Date: 2024-01-16 10:59:38
LP-533401 hydrochloride is a tryptophan hydroxylase 1 inhibitor that regulates serotonin production in the gut.

Name	L-Phenylalanine, 4-[2-amino-6-[2,2,2-trifluoro-1-(3'-fluoro[1,1'-biphenyl]-4-yl)ethoxy]-4-pyrimidinyl]-, hydrochloride (1:1)
Synonyms	L-Phenylalanine, 4-[2-amino-6-[2,2,2-trifluoro-1-(3'-fluoro[1,1'-biphenyl]-4-yl)ethoxy]-4-pyrimidinyl]-, hydrochloride (1:1) 4-{2-Amino-6-[2,2,2-trifluoro-1-(3'-fluoro-4-biphenylyl)ethoxy]-4-pyrimidinyl}-L-phenylalanine hydrochloride (1:1) LP-533401HCl

Description	LP-533401 hydrochloride is a tryptophan hydroxylase 1 inhibitor that regulates serotonin production in the gut.
Related Catalog	Signaling Pathways >> Metabolic Enzyme/Protease >> Tryptophan Hydroxylase Research Areas >> Cardiovascular Disease Research Areas >> Metabolic Disease
Target	Tryptophan hydroxylase 1[1]
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].
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].
Animal Admin	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.

Molecular Formula	C₂₇H₂₃ClF₄N₄O₃
Molecular Weight	562.943
Exact Mass	562.139465
PSA	124.35000
LogP	7.25220
Storage condition	2-8℃

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