Tegaserod maleate (SDZ-HTF-919) 是一种口服有效的 5-羟色胺受体 4 (HTR4;5-HT4R) 激动剂和5-HT2B受体拮抗剂。Tegaserod maleate 对人重组 5-HT2A、5-HT2B和 5-HT2C受体的 pKis 分别为 7.5、8.4 和 7.0。Tegaserod maleate 导致肿瘤细胞凋亡，减弱 PI3K/Akt/mTOR 信号传导并降低 S6 磷酸化。Tegaserod maleate 具有抗肿瘤活性，同时具有用于肠易激综合征 (IBS) 研究的潜力。
| 生物活性 | Tegaserod maleate (SDZ-HTF-919) is an orally activeserotonin receptor 4(HTR4;5-HT4R) agonist and a5-HT2Breceptor antagonist. Tegaserod maleate has pKis of 7.5, 8.4 and 7.0 for human recombinant 5-HT2A, 5-HT2Band 5-HT2Creceptors, respectively. Tegaserod maleate causes tumor cellapoptosis, bluntsPI3K/Akt/mTORsignaling and decreases S6 phosphorylation. Tegaserod maleate has anti-tumor activity and has the potential for irritable bowel syndrome (IBS) research[1][2][3]. |
| IC50& Target | 5-HT4Receptor | 5-HT2BReceptor |
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体外研究
(In Vitro) | 马来酸替加色罗 (SDZ-HTF-919; 3-5 μM; 24-72 小时) 引起显着的时间和剂量依赖性细胞凋亡增加[1]。
马来酸替加色罗 (3-5 μM; 8-18 小时) 降低 p-S6 ，p-p70 S6 (Thr421/Ser424)[1]。
马来酸替加色罗 (0.1-3 μM; 24 小时) 有效抑制 5-HT 介导的大鼠离体胃底收缩 (pA2=8.3)，与 5-HT2B受体拮抗剂活性一致[3]。
Apoptosis Analysis[1] | Cell Line: | A375, RPMI-7951 (RPMI), SH4, B16F10, MeWo and MEL-JUSO | | Concentration: | 3, 5 μM | | Incubation Time: | 24, 48, 72 h | | Result: | There was a significant time and dose-dependent increase in apoptosis in all cell lines. |
Western Blot Analysis[1] | Cell Line: | RPMI, SH4 and B16F10 cells | | Concentration: | 3, 5 μM | | Incubation Time: | 8 or 18 h | | Result: | Decreased phosphorylation of the kinase directly upstream of S6, p70 S6 at Thr421/Ser424. |
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体内研究
(In Vivo) | 马来酸替加色罗 (SDZ-HTF-919; 5 mg/kg/天; 腹腔注射; 连续五天) 在体内延迟肿瘤生长、减少转移、增加存活率并抑制 p-S6[1]。
马来酸替加色罗 (0.1-2.0 mg/kg; 胃负荷前 15 分钟腹腔注射) 显着加速 db/db 小鼠的胃葡萄糖排空率，在 0.1mg/kg 的情况下将 30 分钟时留在胃中的膳食部分减少 80%[2].
| Animal Model: | C57BL/6 J mice were subcutaneously injected with B16F10 cells[1] | | Dosage: | 5 mg/kg | | Administration: | Administered intraperitoneally (i.p.) daily for five consecutive days | | Result: | Treatment significantly decreased tumor growth and resulted in only slight decreases in weight following treatment. |
| Animal Model: | Female C57BLKS/J db/db mice[2] | | Dosage: | 0.1, 0.5, 1.0, 2.0 mg/kg | | Administration: | IP; 15 min prior to gastric loading | | Result: | Produced a dramatic decrease in the fraction of the meal remaining in the stomach for doses as low as 0.1 mg/kg (0.1 mg/kg).
Accelerated gastric emptying, with a reduction of nearly 80% in the fraction remaining at 30 min (P< 0.0001) (0.1 mg/kg).
Induced a significant decrease in the gastric emptying rate as the amount of the meal remaining at 30 min was significantly greater (2.0 mg/kg).
Resulted in inhibition of tegaserod-induced increased gastric emptying (0.1 mg/kg).
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | 4°C, sealed storage, away from moisture *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture) |
| 溶解性数据 | In Vitro: DMSO : ≥ 35 mg/mL(83.84 mM) H2O : 1 mg/mL(2.40 mM;Need ultrasonic) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 2.3954 mL | 11.9772 mL | 23.9544 mL | | 5 mM | 0.4791 mL | 2.3954 mL | 4.7909 mL | | 10 mM | 0.2395 mL | 1.1977 mL | 2.3954 mL |
*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℃, 6 months; -20℃, 1 month (sealed storage, away from moisture)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 In Vivo: 请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照In Vitro方式配制澄清的储备液，再依次添加助溶剂： ——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用；
以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶 1. 请依序添加每种溶剂： 10% DMSO 40%PEG300 5%Tween-80 45% saline Solubility: ≥ 2.5 mg/mL (5.99 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.99 mM，饱和度未知) 的澄清溶液。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。 2. 请依序添加每种溶剂： 10% DMSO 90%corn oil Solubility: ≥ 2.5 mg/mL (5.99 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (5.99 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。 以 1 mL 工作液为例，取 100 μL 25.0 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。 *以上所有助溶剂都可在本网站选购。
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