Tegaserod 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 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 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 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 is an orally activeserotonin receptor 4(HTR4;5-HT4R) agonist and a5-HT2Breceptor antagonist. Tegaserod has pKis of 7.5, 8.4 and 7.0 for human recombinant 5-HT2A, 5-HT2Band 5-HT2Creceptors, respectively. Tegaserod causes tumor cellapoptosis, bluntsPI3K/Akt/mTORsignaling and decreases S6 phosphorylation. Tegaserod has anti-tumor activity and has the potential for irritable bowel syndrome (IBS) research[1][2][3]. |
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体外研究
(In Vitro) | 替加色罗 (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]。
替加色罗 (3-5 μM; 8-18 小时) 降低 p-S6 ，p-p70 S6 (Thr421/Ser424)[1]。
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) | 替加色罗 (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]。
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 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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