Telotristat ethyl (formerly LX-1032; LX-1606; LX-1032; LX-1606; trade name: Xermelo), the ethyl ester prodrug form of Telotristat, is an orally bioavailable tryptophan hydroxylase (TPH) inhibitor (IC50 = 0.028 μM) with antiserotonergic and anti-diarrhea activity. As of 2017, Telotristat ethyl has been approved to treat carcinoid syndrome diarrhea. 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.
理化性质和储存条件
| Molecular Weight (MW) | 574.99 |
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| Formula | C27H26ClF3N6O3 |
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| CAS No. | 1033805-22-9 (Telotristat ethyl); |
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| Storage | -20℃ for 3 years in powder form |
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| -80℃ for 2 years in solvent |
| Solubility (In vitro) | DMSO: ≥ 100 mg/mL |
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| Water: N/A |
| Ethanol: N/A |
| Solubility (In vivo) | O=C(OCC)[C@@H](N)CC1=CC=C(C2=NC(N)=NC(O[C@H](C3=CC=C(Cl)C=C3N4N=C(C)C=C4)C(F)(F)F)=C2)C=C1 |
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| Synonyms | LX 1032; LX 1606; LX-1032; LX1606; LX1032; LX-1606; trade name: Xermelo |
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实验参考方法
| In Vitro | In vitro activity: 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. |
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| In 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. |
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| Animal model | Male C57BL/6 mice and male C57 albino mice. |
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| Formulation & Dosage | Dissolved in 15% cyclodextrin or 0.25% methylcellulose; 300 mg/kg; p.o. |
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| References | Gut. 2014 Jun;63(6):928-37. |
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