Telotristat

Names

[ Name ]:
Telotristat

[Synonym ]:
LP778902
(S)-2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)-phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoic acid
(S)-2-amino-3-(4-(2-amino-6-((R)-1-(4-chloro-2-(3-methyl-1H-pyrazol-1-yl)phenyl)-2,2,2-trifluoroethoxy)pyrimidin-4-yl)phenyl)propanoic acid
(S)-2-amino-3-[4-(2-amino-6-{(R)-1-[4-chloro-2-(3-methylpyrazol-1-yl)phenyl]-2,2,2-trifluoroethoxy}pyrimidine-4-yl)phenyl]propionic acid
(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

Biological Activity

[Description]:

Telotristat (LP-778902) is a potent tryptophan hydroxylase inhibitor with an in vivo IC50 of 0.028 μM.

[Related Catalog]:

Signaling Pathways >> Metabolic Enzyme/Protease >> Tryptophan Hydroxylase

Research Areas >> Neurological Disease

[Target]

IC50: 0.028 μM (tryptophan hydroxylase)[1]

[In Vitro]

Telotristat is the active moiety of telotristat etiprate. Telotristat etiprate is an ethyl ester prodrug which is hydrolyzed to telotristat. Telotristat etiprate is orally available serotonin synthesis inhibitor for the treatment of carcinoid syndrome[1].

[In Vivo]

Telotristat etiprate is present in very low levels after oral administration. These low levels are due to rapid hydrolysis into the active moiety telotristat. The half-life ranges from approximately 4-12 h. There is no accumulation of telotristat with multiple dose administration over 2 weeks. Exposure to telotristat is approximately dose proportional[1].

[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[2].

[Animal admin]

Rats: 14-week-old male C57 albino mice are dosed once daily by oral gavage at 5-10 mL/kg for four consecutive days. Five hours after the last dose, the animals are quickly sacrificed. 5-HT is extracted from the blood or tissues and measured by HPLC. Blood samples are taken for exposure analysis[2].

[References]

[1]. Lapuerta P, et al. Telotristat etiprate, a novel inhibitor of serotonin synthesis for the treatment of carcinoid syndrome. Clin. Invest. (Lond.) (2015) 5(5), 447–456

[2]. US20080153852

[Related Small Molecules]

DL-4-Chlorophenylalanine | LX-1031 | LP-533401 | Telotristat

Chemical & Physical Properties

[ Density]:
1.50±0.1 g/cm3 (20 ºC 760 Torr), 计算值

[ Molecular Formula ]:
C₂₅H₂₂ClF₃N₆O₃

[ Molecular Weight ]:
546.92900

[ Exact Mass ]:
546.13900

[ PSA ]:
142.17000

[ LogP ]:
5.79160

[ Storage condition ]:
2-8℃

Precursor & DownStream

Precursor

DownStream

Related Compounds

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