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5mg |
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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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Purity: ≥98%
Telotristat Etiprate (LX1606 etiprate; LX1032; LX-1032; LX-1606) is the hippurate salt of telotristat ethyl, which is a prodrug of Telotristat. Telotristat ethyl (trade name: Xermelo) is an orally bioavailable and peripheral tryptophan hydroxylase (TPH) inhibitor with potential antiserotonergic activity. Telotristat etiprate is converted under in vivo condition to the active form, telotristat (LP-778902), which binds to and inhibits the activity of TPH. Telotristat etiprate is useful in controlling diarrhea associated with carcinoid syndrome. Telotristat Etiprate acts by inhibiting the enzyme tryptophan hydoxylase (TPH) and reduces serotonin production both inside and outside the GI tract without affecting brain serotonin levels.
Targets |
Tryptophan hydroxylase
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ln Vitro |
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ln Vivo |
Serotonin levels in the peripheral are decreased by telotristat ethyl (15, 50, 150, 300 mg/kg, po, qd), but not in the mouse brain. Telotristat ethyl (200 mg/kg po, qd) significantly protects mice against inflammatory bowel disease and inhibits the rise in blood neutrophil counts seen following TNBS challenge. Histopathological evaluation of a mouse model of IBD confirms that telotristat ethyl (200 mg/kg po, qd) protects the model [1]. In the jejunum, telotristat ethyl (15, 50, 150, and 300 mg/kg) depletes 5-HT, but not in the brain. Nevertheless, neither constitutive gastrointestinal motility nor serotonin (5-HT) depletion of enteric neurons occurs in mice treated with telotristat ethyl (200 mg/kg, po). The severity of colitis caused by trinitrobenzene sulfonic acid (TNBS) is lessened by telotristat ethyl (200 mg/kg) [2].
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Animal Protocol |
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References |
[1]. Tamas Oravecz, et al. LX1606 (aka LX1032), a Novel Inhibitor of Serotonin Synthesis, Alleviates Development of Inflammatory Bowel Disease in a Preclinical Model. (http://assets.cureus.com/uploads/poster/file/46/d.pdf)
[2]. Margolis, K.G., et al., Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine. Gut, 2014 Jun;63(6):928-37. |
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Additional Infomation |
Telotristat Etiprate is an orally bioavailable, small-molecule, tryptophan hydroxylase (TPH) inhibitor prodrug, with potential antiserotonergic activity. Upon administration, telotristat etiprate is converted to its active moiety, telotristat (LP-778902), which binds to and blocks the activity of TPH. This may result in a reduction in peripheral serotonin (5-HT) production and improvement of serotonin-mediated gastrointestinal effects such as severe diarrhea. TPH, the rate-limiting enzyme in serotonin biosynthesis, is overexpressed in carcinoid tumor cells.
Xermelo is indicated for the treatment of carcinoid syndrome diarrhoea in combination with somatostatin analogue (SSA) therapy in adults inadequately controlled by SSA therapy. |
Molecular Formula |
C27H26N6O3F3CL.C9H9NO3
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Molecular Weight |
754.154600000001
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Exact Mass |
753.2289
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Elemental Analysis |
C, 57.33; H, 4.68; Cl, 4.70; F, 7.56; N, 13.00; O, 12.73
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CAS # |
1137608-69-5
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Related CAS # |
Telotristat ethyl;1033805-22-9;Telotristat;1033805-28-5; 1137608-69-5 (etiprate) ; 1374745-52-4 (besilate)
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PubChem CID |
25253377
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Appearance |
White to off-white solid powder
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Melting Point |
145 °C
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LogP |
7.16
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tPSA |
197.57
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InChi Key |
XSFPZBUIBYMVEA-CELUQASASA-N
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InChi Code |
InChI=1S/C27H26ClF3N6O3.C9H9NO3/c1-3-39-25(38)20(32)12-16-4-6-17(7-5-16)21-14-23(35-26(33)34-21)40-24(27(29,30)31)19-9-8-18(28)13-22(19)37-11-10-15(2)36-37;11-8(12)6-10-9(13)7-4-2-1-3-5-7/h4-11,13-14,20,24H,3,12,32H2,1-2H3,(H2,33,34,35);1-5H,6H2,(H,10,13)(H,11,12)/t20-,24+;/m0./s1
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Chemical Name |
2-benzamidoacetic acid;ethyl (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]propanoate
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
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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) |
Solubility in Formulation 1: ≥ 10 mg/mL (13.26 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 100.0 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: ≥ 10 mg/mL (13.26 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 100.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.  (Please use freshly prepared in vivo formulations for optimal results.) |
Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
1 mM | 1.3260 mL | 6.6300 mL | 13.2600 mL | |
5 mM | 0.2652 mL | 1.3260 mL | 2.6520 mL | |
10 mM | 0.1326 mL | 0.6630 mL | 1.3260 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.
NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
NCT03442725 | Completed Has Results | Drug: Telotristat etiprate | Renal Impairment | Ipsen | February 9, 2018 | Phase 1 |
NCT02026063 | Completed Has Results | Drug: Telotristat etiprate | Carcinoid Syndrome | Lexicon Pharmaceuticals | January 14, 2014 | Phase 3 |
NCT02063659 | Completed Has Results | Drug: Telotristat etiprate Drug: Placebo |
Carcinoid Syndrome | Lexicon Pharmaceuticals | March 11, 2014 | Phase 3 |
NCT01104415 | Completed Has Results | Drug: Telotristat etiprate | Carcinoid Syndrome | Lexicon Pharmaceuticals | June 15, 2010 | Phase 2 |