LX-1031TPH inhibitor CAS# 945976-76-1 |
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| Cas No. | 945976-76-1 | SDF | Download SDF |
| PubChem ID | 23633604 | Appearance | Powder |
| Formula | C28H25F3N4O4 | M.Wt | 538.52 |
| Type of Compound | N/A | Storage | Desiccate at -20°C |
| Solubility | DMSO : ≥ 34 mg/mL (63.14 mM) *"≥" means soluble, but saturation unknown. | ||
| Chemical Name | (2S)-2-amino-3-[4-[2-amino-6-[(1R)-2,2,2-trifluoro-1-[4-(3-methoxyphenyl)phenyl]ethoxy]pyrimidin-4-yl]phenyl]propanoic acid | ||
| SMILES | COC1=CC=CC(=C1)C2=CC=C(C=C2)C(C(F)(F)F)OC3=NC(=NC(=C3)C4=CC=C(C=C4)CC(C(=O)O)N)N | ||
| Standard InChIKey | XNMUICFMGGQSMZ-WIOPSUGQSA-N | ||
| Standard InChI | InChI=1S/C28H25F3N4O4/c1-38-21-4-2-3-20(14-21)17-9-11-19(12-10-17)25(28(29,30)31)39-24-15-23(34-27(33)35-24)18-7-5-16(6-8-18)13-22(32)26(36)37/h2-12,14-15,22,25H,13,32H2,1H3,(H,36,37)(H2,33,34,35)/t22-,25+/m0/s1 | ||
| General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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| About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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| Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. | ||
| Description | LX-1031 is an oral, small molecule inhibitor of tryptophan 5-hydroxylase (TPH). | |||||
| Targets | TPH | |||||
LX-1031 Dilution Calculator
LX-1031 Molarity Calculator
| 1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
| 1 mM | 1.8569 mL | 9.2847 mL | 18.5694 mL | 37.1388 mL | 46.4235 mL |
| 5 mM | 0.3714 mL | 1.8569 mL | 3.7139 mL | 7.4278 mL | 9.2847 mL |
| 10 mM | 0.1857 mL | 0.9285 mL | 1.8569 mL | 3.7139 mL | 4.6424 mL |
| 50 mM | 0.0371 mL | 0.1857 mL | 0.3714 mL | 0.7428 mL | 0.9285 mL |
| 100 mM | 0.0186 mL | 0.0928 mL | 0.1857 mL | 0.3714 mL | 0.4642 mL |
| * Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. | |||||
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Tryptophan hydroxylase (TPH) is a key enzyme in the synthesis of serotonin. Serotonin plays important physiological roles both peripherally and centrally. LX-1031 is a heterocyclic substituted phenylalanine analog, an oral small molecule tryptophan hydroxylase (TPH) inhibitor that reduces synthesis of serotonin (5-HT) peripherally and is being developed for conditions characterized by excess 5-HT expression such as diarrhea-predominant irritable bowel syndrome (IBS-D) and, possibly, carcinoid diarrhea.
In vitro: LX-1031 inhibits TPH1 at its concentration of 10-8–10-7 mol L-1 range [1].
In vivo: With oral administration of LX-1031 in mice, the 5-HT reductions in the jejunum relative to control were ~33%, 51%, and 66% with the 15, 45 and 135 mg/kg/day doses, respectively; the effect of 5 mg/kg/day on GI 5-HT content was not significantly different from control [2].
Clinical trial: In double-blind studies (doses of LX-1031 ranging from 250 to 1000 mg q.i.d.), average 5HIAA reductions of 33% were noted. In phase I studies, 54 healthy volunteers received the drug for up to 14 days while the diet was strictly controlled to avoid 5-HT-rich foods. Twenty four hour urine collections were obtained. Significant reductions in urinary 5-HIAA persisted over the duration of exposure [3].
References:
[1] Camilleri M. LX-1031, a tryptophan 5-hydroxylase inhibitor, and its potential in chronic diarrhea associated with increased serotonin. Neurogastroenterol Motil. 2011;23(3):193-200.
[2] Brown PM, Jackson JI, Frazier KS, Turner CA, Shi ZC, Liu Q. From mouse knockout to investigational drug: LX1031, a novel potential treatment for irritable bowel syndrome. Am J Gastroenterol 2007; 102: S961 (Abstract).
[3] Freiman J, Jackson J, Frazier KS, Yang QM, Liu Q, Brown P. LX1031: inhibition of 5-HT synthesis as a new target in the management of irritable bowel syndrome (IBS). Neurogastroenterol Motil 2009; 21: 250.
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LX-1031, a tryptophan 5-hydroxylase inhibitor, and its potential in chronic diarrhea associated with increased serotonin.[Pubmed:21159063]
Neurogastroenterol Motil. 2011 Mar;23(3):193-200.
LX-1031 is an oral, small molecule tryptophan 5-hydroxylase (TPH) inhibitor that reduces serotonin (5-HT) synthesis peripherally. It has potential for illnesses characterized by excess 5-HT, such as diarrhea-predominant irritable bowel syndrome (IBS-D) and carcinoid diarrhea. In vitro, inhibition of TPH1 occurred in 10(-8) -10(-7) mol L(-1) range. In vivo in rodents, LX-1031 has no effect on brain 5-HT while dose-dependently reducing 5-HT, particularly in the small bowel. After oral LX1031 in humans, systemic exposure is very low, plasma concentrations are linear in dose range 250-750 mg q.i.d.; the median T(1/2) for elimination is approximately 20 h, and repeat administration for 14 days doubles C(max) . In ascending-single-dose and multiple-dose (14 days) trials in healthy volunteers, LX-1031, 2-4 g day(-1) significantly reduced urinary 5-hydroxyindoleacetic acid (5-HIAA) starting by Day 5, and persisting over the 14 day exposure. There are no dose-limiting toxicities in healthy subjects or remarkable adverse effects in clinical trials to date. Over a 28-day treatment period, LX-1031 was associated with improved weekly global scores (2/4 weeks) and improved stool consistency with lower urinary 5-HIAA excretion. LX-1031 appears promising for chronic diarrhea associated with increased 5-HT expression including IBS-D. Optimal doses, efficacy and safety in IBS clinical trials need to be fully elucidated; low systemic exposure, selectivity for TPH1 over TPH2, and lack of effect on brain 5-HT in several species suggest that LX-1031 is unlikely to cause affective disorders.
LX-1031, a tryptophan 5-hydroxylase inhibitor that reduces 5-HT levels for the potential treatment of irritable bowel syndrome.[Pubmed:21154152]
IDrugs. 2010 Dec;13(12):921-8.
LX-1031, being developed by Lexicon Pharmaceuticals, is an oral, small-molecule tryptophan 5-hydroxylase (TPH) inhibitor that reduces 5-HT synthesis peripherally. LX-1031 is being developed for the potential treatment of diarrhea-predominant irritable bowel syndrome (IBS-D), which is characterized by excess 5-HT. In preclinical studies, LX-1031 dose-dependently reduced expression of 5-HT in the duodenum, jejunum and ileum, but had no effect on brain 5-HT levels. In ascending single-dose and multiple-dose (14 day) phase I clinical trials in healthy volunteers, LX-1031 significantly reduced urinary 5-hydroxyindoleacetic acid (5-HIAA; a marker of 5-HT metabolism) levels, starting by day 5 and persisting over the duration of exposure. In a phase II clinical trial in patients with IBS-D, a 1000-mg qid dose of LX-1031 was associated with improved weekly global scores and stool consistency, and lower urinary 5-HIAA levels over a 28-day treatment period. LX-1031 was well tolerated in trials to date. In conclusion, LX-1031 appears promising for IBS-D. Optimal doses, efficacy in IBS clinical trials and safety need to be fully elucidated.
