LX1606 Hippurate (Telotristat etiprate)
(Synonyms: 特罗司他马尿酸盐; LX1606 Hippurate) 目录号 : GC10007
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Telotristat etiprate 是一种乙酯前药，可在体内和体外水解为其活性部分 LP-778902。
Cas No.:1137608-69-5
Sample solution is provided at 25 µL, 10mM.
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Telotristat etiprate is an ethyl ester prodrug which is hydrolyzed to its active moiety LP-778902 both in vivo and in vitro. Systemic exposure of Telotristat etiprate is relatively low, as the hydrolysis to the active moiety is rapid. LP-778902 is a potent inhibitor of TPH with an in vivo IC50 of 0.028 μM.[2]
In normal mice, Telotristat etiprate (administered once daily for 4 days at doses of 15-300 mg/kg/day) was found to reduce serotonin levels throughout the gastro-intestinal tract. These reductions occurred in a dose-dependent fashion with maximal effects observed with doses of Telotristat etiprate ≥150 mg/kg. No significant change in brain serotonin or 5-hydroxyindoleacetic acid (5-HIAA, a serotonin metabolite) was observed. Similar findings were seen in Sprague-Dawley rats. [1, 2]
Gastrointestinal motility studies were conducted in rat using the charcoal meal teat. There was a significant dose-related delay in both gastrointestinal transit and gastric emptying, associated with a reduction in blood serotine levels and proximal colon serotonin. [2]
Telotristat etiprate and its active moiety LP-778902 were tested for their inhibition of two related enzymes, phenylalanine and tyrosine hydroxylase, as well as several cytochrome P450 isoenzymes. This demonstrated that Telotristat etiprate is a highly specific inhibitor of TPH. [2]
References:
[1]. Margolis, Kara Gross et al. Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine. Gut vol. 63,6 (2014): 928-37.
[2]. Lapuerta, P et al. Telotristat etiprate, a novel inhibitor of serotonin synthesis for the treatment of carcinoid syndrome. Clinical Investigation 2015 Vol.5 No.5 pp.447-456 ref.20
Telotristat etiprate 是一种乙酯前药,可在体内和体外水解为其活性部分 LP-778902。 Telotristat etiprate 的全身暴露相对较低,因为对活性部分的水解是快速的。 LP-778902 是一种有效的 TPH 抑制剂,体内 IC50 为 0.028 μM。[2]
在正常小鼠中,发现 Telotristat etiprate（每天给药一次,剂量为 15-300 mg/kg/天,持续 4 天）可降低整个胃肠道的血清素水平。这些减低以剂量依赖方式发生,用 Telotristat etiprate ≥150 mg/kg 剂量观察到最大效应。未观察到脑血清素或 5-羟基吲哚乙酸（5-HIAA,一种血清素代谢物）的显着变化。在 Sprague-Dawley 大鼠中也观察到类似的发现。 [1, 2]
使用木炭餐奶嘴对大鼠进行了胃肠动力研究。胃肠道转运和胃排空均有显着的剂量相关延迟,这与血液血清素水平和近端结肠血清素的降低有关。 [2]
测试了 Telotristat etiprate 及其活性部分 LP-778902 对两种相关酶（苯丙氨酸和酪氨酸羟化酶）以及几种细胞色素 P450 同工酶的抑制作用。这表明 Telotristat etiprate 是一种高度特异性的 TPH 抑制剂。 [2]
| Animal experiment [1]: | |
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Animal models |
Male C57BL/6 mice, male C57 albino mice |
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Preparation Method |
Two peripheral TPH inhibitors, LP-920540 and telotristat etiprate were given orally to mice. Effects were measured on 5-HT levels in the gut, blood and brain, 5-HT immunoreactivity in the ENS, gastrointestinal motility and severity of trinitrobenzene sulfonic acid (TNBS)-induced colitis. |
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Dosage form |
15, 50, 150, 300 mg/kg, Administered intragastrically |
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Applications |
Telotristat etiprate reduced 5-HT significantly in the gut and blood but not in the brain. Telotristat etiprate cannot decrease 5-HT immunoreactive neurons or fibres in the myenteric plexus or altered total gastrointestinal transit time, colonic motility or gastric emptying in mice. |
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References: [1]. Margolis, Kara Gross et al. Pharmacological reduction of mucosal but not neuronal serotonin opposes inflammation in mouse intestine. Gut vol. 63,6 (2014): 928-37. [2]. Lapuerta, P et al. Telotristat etiprate, a novel inhibitor of serotonin synthesis for the treatment of carcinoid syndrome. Clinical Investigation 2015 Vol.5 No.5 pp.447-456 ref.20 |
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| Cas No. | 1137608-69-5 | SDF | |
| 别名 | 特罗司他马尿酸盐; LX1606 Hippurate | ||
| 化学名 | 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 | ||
| Canonical SMILES | CCOC(=O)C(CC1=CC=C(C=C1)C2=CC(=NC(=N2)N)OC(C3=C(C=C(C=C3)Cl)N4C=CC(=N4)C)C(F)(F)F)N.C1=CC=C(C=C1)C(=O)NCC(=O)O | ||
| 分子式 | C36H35ClF3N7O6 | 分子量 | 754.17 |
| 溶解度 | DMF: 50 mg/ml,DMSO: 50 mg/ml,DMSO:PBS(pH 7.2) (1:2): 0.33 mg/ml,Ethanol: 5 mg/ml | 储存条件 | Store at -20°C, protected from light |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.326 mL | 6.6298 mL | 13.2596 mL |
| 5 mM | 265.2 μL | 1.326 mL | 2.6519 mL |
| 10 mM | 132.6 μL | 663 μL | 1.326 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >99.50% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet