Trimetrexate (CI-898) isethionate 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 isethionate 也能抑制多种癌细胞的生长。Trimetrexate isethionate 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) isethionate 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 isethionate can also inhibit the growth of variouscancercells. Trimetrexate isethionate can be used for researchingPneumocystis cariniipneumonia (PCP) andcancer[1][2][3][4][5]. |
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体外研究
(In Vitro) | Trimetrexate isethionate (0.1 μM; 18 h) completely inhibits proliferation of toxoplasma in murine macrophages[3].
Trimetrexate isethionate (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) isethionate 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) isethionate 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 | Please store the product under the recommended conditions in the Certificate of Analysis. |
