| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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| 500mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
Tryptophan hydroxylase
Telotristat besilate targets tryptophan hydroxylase (TPH), the rate-limiting enzyme in serotonin biosynthesis. It is a potent inhibitor with an in vivo IC₅₀ of 0.028 μM. By inhibiting TPH, it reduces the production of serotonin in the gastrointestinal tract without affecting brain serotonin levels. This reduces the diarrhea and other symptoms associated with carcinoid syndrome. |
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| ln Vitro |
Telotristat (formerly known as LP-778902) is the active metabolite of LX1606 (Telotristat etiprate) which is an orally bioavailable, small-molecule, tryptophan hydroxylase (TPH) inhibitor with potential an in vivo IC50 of 0.028 μM and with antiserotonergic activity. Telotristat has activity in controlling diarrhea associated with carcinoid syndrome. Telotristat acts by inhibiting the enzyme tryptophan hydoxylase (TPH) and reduces serotonin production both inside and outside the GI tract without affecting brain serotonin levels. Blocking peripheral serotonin synthesis by telotristat reduces severity of both chemical- and infection-induced intestinal inflammation.
Kinase Assay: Telotristat (formerly known as LP-778902) is the active metabolite of LX1606 (Telotristat etiprate) which is an orally bioavailable, small-molecule, tryptophan hydroxylase (TPH) inhibitor with potential an in vivo IC50 of 0.028 μM and with antiserotonergic activity. Cell Assay: BON CBA cells are grown in equal volume of DMEM and F12K with 5% bovine serum for 3-4 hours (20 K cell/well) and telotristat is added at a concentration range of 0.07 to 50 μM. The cells are incubated at 37°C overnight. 50 μM of the culture supernatant is then taken for 5HTP measurement. The supernatant is mixed with equal volume of 1M TCA, then filtered through glass fiber. The filtrate is loaded on reverse phase HPLC for 5HTP concentration measurement. The cell viability is measured by treating the remaining cells with Celltiter-Glo Luminescent Cell Viability Assay. In vitro, Telotristat besilate is a potent TPH inhibitor. It inhibits serotonin production in enterochromaffin cells. Its activity is measured by the reduction of serotonin levels in cell culture supernatants. It shows selectivity for peripheral TPH over central TPH. |
| ln Vivo |
LX1606 (LX 1606, LX-1606) is useful for Neurological Disease. LX1606 were given orally to mice. LX1606 reduced 5-HT significantly in the gut and blood but not in the brain. oral LX1032 reduced the severity of TNBS-induced colitis; the expression of 24% of 84 genes encoding inflammation-related cytokines and chemokines was lowered at least fourfold and the reduced expression of 17% was statistically significant [1]. Treatment with LX1606 showed a strong positive effect in ameliorating TNBS-induced IBD in mice as assessed by various parameters of disease development. These preclinical data demonstrate that inhibition of TPH activity by LX1606 may provide a new approach for the treatment of IBD and its serotonin-mediated symptoms. |
| Enzyme Assay |
In vitro TPH enzyme assays for Telotristat besilate involve measuring the conversion of tryptophan to 5-hydroxytryptophan (5-HTP) by TPH in the presence of varying concentrations of the inhibitor. The enzyme is incubated with tryptophan and cofactors, and the production of 5-HTP is measured by HPLC or LC-MS. IC₅₀ values are calculated from dose-response curves.
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| Cell Assay |
In vitro cell-based assays for Telotristat besilate are performed using enterochromaffin cells or cell lines that express TPH and produce serotonin. Cells are cultured in appropriate media and treated with Telotristat besilate at various concentrations. Serotonin levels in the culture medium are measured by ELISA. Cell viability is assessed by MTT assays.
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| Animal Protocol |
Dissolved in 15% cyclodextrin or 0.25% methylcellulose; 300 mg/kg; p.o. | Male C57BL/6 mice and male C57 albino mice.
| ADME/Pharmacokinetics |
Telotristat besilate is the active moiety of the prodrug Telotristat etiprate. Specific pharmacokinetic properties are characteristic of the prodrug. It is administered orally and is absorbed from the gastrointestinal tract. It is metabolized in the liver and excreted primarily in feces.
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| Toxicity/Toxicokinetics |
Telotristat besilate is generally well-tolerated. Common adverse effects include nausea, headache, and increased liver enzymes. It is contraindicated in patients with known hypersensitivity to Telotristat. As an approved drug, it is available by prescription for the treatment of carcinoid syndrome diarrhea.
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| References |
Gut.2014 Jun;63(6):928-37.
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| Additional Infomation |
Telotristat besilate is a potent TPH inhibitor. It is the active moiety of the FDA-approved prodrug Telotristat etiprate (Xermelo®). It is used to control diarrhea associated with carcinoid syndrome. This product is for human therapeutic use.
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| Molecular Formula |
C31H28CLF3N6O6S
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| Molecular Weight |
705.1
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| Exact Mass |
704.143
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| Elemental Analysis |
C, 52.81; H, 4.00; Cl, 5.03; F, 8.08; N, 11.92; O, 13.61; S, 4.55
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| CAS # |
1374745-52-4
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| Related CAS # |
1137608-69-5 (etiprate);1033805-22-9 (ethyl);1033805-28-5 (acid);1374745-52-4 (besilate);
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| PubChem CID |
56962367
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| Appearance |
Typically exists as solid at room temperature
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
48
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| Complexity |
974
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| Defined Atom Stereocenter Count |
2
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| SMILES |
S(C1C=CC=CC=1)(O)(=O)=O.[C@@H](C1C=CC(Cl)=CC=1N1N=C(C)C=C1)(C(F)(F)F)OC1=NC(N)=NC(C2C=CC(C[C@H](N)C(=O)O)=CC=2)=C1
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| InChi Key |
WYZQOTLDKIRRDC-VNJAQMQMSA-N
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| InChi Code |
InChI=1S/C25H22ClF3N6O3.C6H6O3S/c1-13-8-9-35(34-13)20-11-16(26)6-7-17(20)22(25(27,28)29)38-21-12-19(32-24(31)33-21)15-4-2-14(3-5-15)10-18(30)23(36)37;7-10(8,9)6-4-2-1-3-5-6/h2-9,11-12,18,22H,10,30H2,1H3,(H,36,37)(H2,31,32,33);1-5H,(H,7,8,9)/t18-,22+;/m0./s1
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| Chemical Name |
(2S)-2-amino-3-[4-[2-amino-6-[(1R)-1-[4-chloro-2-(3-methylpyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy]pyrimidin-4-yl]phenyl]propanoic acid;benzenesulfonic acid
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.4182 mL | 7.0912 mL | 14.1824 mL | |
| 5 mM | 0.2836 mL | 1.4182 mL | 2.8365 mL | |
| 10 mM | 0.1418 mL | 0.7091 mL | 1.4182 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
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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