|LP533401 hclTph-1 inhibitor|
Sample solution is provided at 25 µL, 10mM.
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|Cas No.||1040526-12-2||SDF||Download SDF|
|Chemical Name||(2S)-2-amino-3-(4-(2-imino-6-(2,2,2-trifluoro-1-(3'-fluoro-[1,1'-biphenyl]-4-yl)ethoxy)-2,3-dihydropyrimidin-4-yl)phenyl)propanoic acid hydrochloride|
|Solubility||Soluble in DMSO||Storage||Store at -20°C|
LP533401 hcl is an inhibitor of Tph-1 .
Tryptophan hydroxylase-1 (Tph-1) is an isoenzyme of tryptophan hydroxylase and the initial enzyme in gut- and lung-derived serotonin biosynthesis. Tph-1 is mainly expressed in the gut and lung .
LP533401 hcl is a Tph-1 inhibitor. In rat RBL2H3 cells expressing Tph1, LP533401 (1 μM) completely inhibited serotonin production. LP533401 reduced the activity of recombinant wild-type TPH-1 by 70% by interacting with residues Tyr235 and Phe241 .
In rodents, LP533401 orally administration was incapable of crossing the blood-brain barrier. In mice, LP533401 (250 mg/kg) dose-dependently reduced serum serotonin concentration by 30%. In ovariectomized female C57BL6/J mice, LP533401 (10, 100, 250 mg/kg for 28 days) increased bone mass and bone-formation parameters such as osteocalcin serum concentration, osteoblast numbers and bone formation rate. Also, LP533401 dose-dependently decreased serum serotonin concentration but didn’t affect brain serotonin content. In ovariectomized female rats, LP533401 completely rescued the ovariectomy-induced osteopenia . In transgenic SM22-5-HTT+ mice overexpressing 5-HT transporter (5-HTT) in smooth muscle cells and spontaneously developing pulmonary hypertension (PH), LP533401 (250 mg/kg for 21 days) significantly reduced lung and blood 5-HT levels, vascular Ki67-positive cells, distal pulmonary artery muscularization, right ventricular (RV) hypertrophy and RV systolic pressure .
. Yadav VK, Balaji S, Suresh PS, et al. Pharmacological inhibition of gut-derived serotonin synthesis is a potential bone anabolic treatment for osteoporosis. Nat Med, 2010, 16(3): 308-312.
. Abid S, Houssaini A, Chevarin C, et al. Inhibition of gut- and lung-derived serotonin attenuates pulmonary hypertension in mice. Am J Physiol Lung Cell Mol Physiol, 2012, 303(6): L500-508.