LP-533401

Names

[ Name ]:
LP-533401

[Synonym ]:
lp-533401 (free base)
(S)-2-Amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(3'-fluorobiphenyl-4-yl)ethoxy]pyrimidin-4-yl}phenyl)propionic acid
4-{2-Amino-6-[2,2,2-trifluoro-1-(3'-fluoro-4-biphenylyl)ethoxy]-4-pyrimidinyl}-L-phenylalanine
L-Phenylalanine, 4-[2-amino-6-[2,2,2-trifluoro-1-(3'-fluoro[1,1'-biphenyl]-4-yl)ethoxy]-4-pyrimidinyl]-
4-{2-Amino-6-[2,2,2-trifluoro-1-(3'-fluorobiphenyl-4-yl)ethoxy]pyrimidin-4-yl}-L-phenylalanine
lp 533401
(2S)-2-Amino-3-{4-{2-amino-6-{2,2,2-trifluoro-1-[3'-fluoro-(1,1'-biphenyl)-4-yl]ethoxy}pyrimidin-4-yl}phenyl}propanoic acid
LP-533401

Biological Activity

[Description]:

LP-533401 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]

[In Vitro]

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

[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[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].

[Animal admin]

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].

[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.

[Related Small Molecules]

Telotristat | DL-4-Chlorophenylalanine | LX-1031 | LP533401 HCI

Chemical & Physical Properties

[ Density]:
1.4±0.1 g/cm3

[ Boiling Point ]:
699.0±65.0 °C at 760 mmHg

[ Molecular Formula ]:
C₂₇H₂₂F₄N₄O₃

[ Molecular Weight ]:
526.482

[ Flash Point ]:
376.5±34.3 °C

[ Exact Mass ]:
526.162781

[ PSA ]:
124.35000

[ LogP ]:
5.62

[ Vapour Pressure ]:
0.0±2.3 mmHg at 25°C

[ Index of Refraction ]:
1.609

[ Storage condition ]:
2-8℃

Related Compounds

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