| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 25mg |
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| 50mg | |||
| 100mg | |||
| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
LP-533401 targets tryptophan hydroxylase 1 (TPH1), an isoenzyme of tryptophan hydroxylase responsible for serotonin biosynthesis in peripheral tissues such as the gut and lungs. By inhibiting TPH1, it selectively reduces peripheral serotonin levels without affecting central serotonin (which is synthesized by TPH2). The compound shows negligible brain exposure due to poor blood-brain barrier penetration.
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| ln Vitro |
LP-533401 Hydrochronide is a tryptophan platformase1. LP-533401 (1 μM) totally suppresses plasmatonin synthesis in Tph1-expressing cells (RBL2H3 cells) after 3 days of treatment [1].
In vitro, LP-533401 effectively suppresses serotonin production at micromolar concentrations in Tph1-expressing cells. At 1 µM, it completely inhibits serotonin production in Tph1-expressing RBL2H3 cells after treatment for 3 days. This demonstrates its potent and selective inhibition of TPH1 in cellular systems. |
| ln Vivo |
Because of a distinct rise in bone mass, LP-533401 (25, 100, or 250 mg/kg) increased intensity once daily for six weeks boosted attempts to avoid and totally rescue osteoporosis in animals in late pregnancy. According to pharmacokinetic studies, LP-533401 is essentially impossible to pass the blood-brain barrier since it reaches very low concentrations in the brain of animals after the epidermis [1]. The 5-HT content of lesions, lungs, and blood significantly decreased in mice given LP-533401 (30–250 mg/kg daily), but not in the brain. Lung and damaged 5-HT levels were lowered by 50% following a single dosage of LP-533401 (250 mg/kg), although blood 5-HT levels did not change, suggesting disruption and lung 5-HT production [2]. Tph-1 LP-533401 treatment of glandular healthy cells resulted in a 30% decrease in circulating hematin levels and a 30% increase in incoming osteoblast counts. When LP-533401 is administered to mice that have had an EL4 cell injection, it can decrease venous circulation, prolong survival, and prevent the decrease of osteoblast quantity and trabecular bone volume [3].
In vivo, oral administration of LP-533401 dose-dependently prevents and reverses osteoporosis in ovariectomized rodents by selectively enhancing bone formation. Repeated treatment markedly reduces serotonin levels in peripheral tissues without affecting central serotonin. These findings support the role of gut-derived serotonin in bone metabolism and the therapeutic potential of TPH1 inhibition. |
| Enzyme Assay |
In cell-free enzymatic assays, LP-533401's activity is evaluated by measuring its inhibition of TPH1 enzyme activity. The enzyme (recombinant TPH1) is incubated with its substrate, tryptophan, and the cofactor tetrahydrobiopterin (BH4) in the presence of varying concentrations of the compound. The production of 5-hydroxytryptophan (5-HTP) is quantified by HPLC, and the IC50 is calculated from the inhibition curve.
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| Cell Assay |
In vitro cell-based experiments with LP-533401 typically involve Tph1-expressing cells, such as RBL2H3 cells (a rat basophilic leukemia cell line). Cells are treated with various concentrations of the compound (e.g., 1 µM) for up to 3 days. The amount of serotonin produced and secreted into the culture medium is measured by ELISA or HPLC to assess the compound's inhibitory effect.
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| Animal Protocol |
In vivo animal experiments with LP-533401 have been conducted in ovariectomized rodent models to study its effects on bone metabolism. In these studies, animals are administered the compound orally at various doses, and bone mineral density is measured using micro-CT or dual-energy X-ray absorptiometry (DXA). Peripheral serotonin levels in blood and tissues are also measured to confirm target engagement.
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| ADME/Pharmacokinetics |
Pharmacokinetic studies indicate that LP-533401 is orally bioavailable and can be administered via oral gavage. The compound shows negligible brain exposure due to poor blood-brain barrier penetration, which is a desirable property for selectively targeting peripheral serotonin. No detailed PK parameters such as half-life or Cmax are publicly available.
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| Toxicity/Toxicokinetics |
No specific toxicity data is publicly available for LP-533401 HCl. In preclinical studies, the compound was well-tolerated at doses that effectively prevented and reversed osteoporosis in rodents. The compound is for research use only and is not intended for human therapeutic applications. No systemic toxicity studies have been reported in the available literature.
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| References |
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| Additional Infomation |
LP-533401 HCl is a selective TPH1 inhibitor with a molecular formula of C27H23ClF4N4O3 and a molecular weight of 562.94. It is also known as (2S)-2-amino-3-[4-[2-amino-6-[2,2,2-trifluoro-1-[4-(3-fluorophenyl)phenyl]ethoxy]pyrimidin-4-yl]phenyl]propanoic acid;hydrochloride. The compound is a valuable research tool for studying the role of peripheral serotonin in bone metabolism, gastrointestinal function, and cancer. It is not approved for clinical use.
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| Molecular Formula |
C27H23CLF4N4O3
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|---|---|
| Molecular Weight |
562.94 Exact Mass
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| Exact Mass |
562.139
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| CAS # |
1040526-12-2
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| Related CAS # |
LP-533401;945976-43-2
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| PubChem CID |
102602704
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
7.252
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
11
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
39
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| Complexity |
759
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| Defined Atom Stereocenter Count |
1
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| 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
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| InChi Key |
BHBWZCUMIXCDPM-CHXZROHQSA-N
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| InChi Code |
InChI=1S/C27H22F4N4O3.ClH/c28-20-3-1-2-19(13-20)16-8-10-18(11-9-16)24(27(29,30)31)38-23-14-22(34-26(33)35-23)17-6-4-15(5-7-17)12-21(32)25(36)37/h1-11,13-14,21,24H,12,32H2,(H,36,37)(H2,33,34,35)1H/t21-,24?/m0./s1
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| Chemical Name |
2(S)-Amino-3-(4-{2-amino-6-[2,2,2-trifluoro-1-(3'-fluoro-biphenyl-4-yl)-ethoxy]-pyrimidin-4-yl}-phenyl)-propionic acid Hydrochloride
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| Synonyms |
LP-533401 HCl LP 533401 HCl LP533401 HCl LP-533401 Hydrochloride LP 533401 Hydrochloride LP533401 Hydrochloride
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~25 mg/mL (~44.41 mM)
H2O : ≥ mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.44 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (4.44 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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