Trimetrexate (CI-898) 是一种抗生素 (antibiotic)，也是一种有效的、具有口服活性的二氢叶酸还原酶 (DHFR) 抑制剂，减少 DNA 和 RNA 前体的产生并导致细胞死亡，对人 DHFR 和刚地弓形虫 (Toxoplasma gondii) DHFR 的IC50分别为 4.74 nM 和 1.35 nM。Trimetrexate 也能抑制多种癌细胞的生长。Trimetrexate 可用于卡氏肺孢子虫肺炎 (PCP) 和癌症的研究。
| 生物活性 | Trimetrexate (CI-898) is anantibiotic, also a potent and orally activedihydrofolate reductase (DHFR)inhibitor, reducing the production of DNA and RNA precursors and leading to cell death, withIC50values of 4.74 nM and 1.35 nM for human DHFR andToxoplasmagondiiDHFR. Trimetrexate can also inhibit the growth of variouscancercells. Trimetrexate can be used for researchingPneumocystis cariniipneumonia (PCP) andcancer[1][2][3][4][5]. |
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体外研究
(In Vitro) | Trimetrexate (0.1 μM, 18 h) completely inhibits proliferation of toxoplasma in murine macrophages[3].
Trimetrexate (1 μM) can cross the toxoplasma cell membrane and rapidly reaches high intracellular concentrations (108 pmol/107cells within 10 min)[3].
Trimetrexate (0.1 mM; 24 h) inhibits cell growth by 50-60% in SNU-C4 and NCI-H630 cell lines[5].
Trimetrexate (1 and 10 mM; 24 h) produces lethality and inhibits DHFR in C4 cells[5].
Cell Proliferation Assay[5] | Cell Line: | SNU-C4 and NCI-H630 | | Concentration: | 0.1 mM | | Incubation Time: | 24 h | | Result: | Inhibited cell growth by 50-60% in both cell lines. |
Cell Proliferation Assay[5] | Cell Line: | C4 cells | | Concentration: | 1 and 10 mM | | Incubation Time: | 24 h | | Result: | Produced 42% and 50% lethality at 1 and 10 mM, respectively. |
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体内研究
(In Vivo) | Trimetrexate (180 mg/kg or 30 mg/kg; p.o. or i.p.; daily) extends the median survival of the toxoplasma infected mice and shows antitoxoplasma activity[3].
Trimetrexate (0-30 mg/kg; i.v.; once daily for 5days) shows chronic toxicity in rats[4].
| Animal Model: | Toxoplasma infected female BALB/c mice weighing about 20 g[3] | | Dosage: | 180 mg/kg or 30 mg/kg | | Administration: | 180 mg/kg per day orally in the drinking water or 30 mg/kg per day i.p. | | Result: | Extended the median survival of the infected mice to 10 d (p.o.) or 19 d (i.p.). |
| Animal Model: | Charles River Wistar Crl(WI)BR rats weighing approximately 150 to 200 g[4] | | Dosage: | 0, 1, 10, or 30 mg/kg | | Administration: | Intravenous injection, once daily for 5 consecutive days followed by a 23-day recovery period | | Result: | Showed chronic toxicity, the testicular changes persisting during the course of multiple cycles of dosing were not reversible within 21 days, but required an additional 56 days for essentially complete recovery. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | | Powder | -20°C | 3 years | | 4°C | 2 years | | In solvent | -80°C | 6 months | | -20°C | 1 month |
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| 溶解性数据 | In Vitro: DMSO : ≥ 61.5 mg/mL(166.48 mM) *"≥" means soluble, but saturation unknown. 配制储备液 | 1 mM | 2.7069 mL | 13.5347 mL | 27.0695 mL | | 5 mM | 0.5414 mL | 2.7069 mL | 5.4139 mL | | 10 mM | 0.2707 mL | 1.3535 mL | 2.7069 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。-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 (6.77 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.77 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 (6.77 mM); Clear solution
此方案可获得 ≥ 2.5 mg/mL (6.77 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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