Trimetrexate isethionate  (Synonyms: CI-898 isethionate)

Trimetrexate (CI-898) isethionate is an antibiotic, also a potent and orally active dihydrofolate reductase (DHFR) inhibitor, reducing the production of DNA and RNA precursors and leading to cell death, with IC₅₀ values of 4.74 nM and 1.35 nM for human DHFR and Toxoplasma gondii DHFR. Trimetrexate isethionate can also inhibit the growth of various cancer cells. Trimetrexate isethionate can be used for researching Pneumocystis carinii pneumonia (PCP) and cancer^{[1][2][3][4][5]}.

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/10⁷ cells 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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

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].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

495.55

C₂₁H₂₉N₅O₇S

82935-04-4

OCCS(=O)(O)=O.NC1=NC(N)=C2C(C)=C(CNC3=CC(OC)=C(OC)C(OC)=C3)C=CC2=N1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Hopper AT, et al. Discovery of Selective Toxoplasma gondii Dihydrofolate Reductase Inhibitors for the Treatment of Toxoplasmosis. J Med Chem. 2019 Feb 14;62(3):1562-1576.  [Content Brief]

  [2]. Fulton, B., et al. Trimetrexate. Drugs 49, 563–576 (1995).  [Content Brief]

  [3]. Allegra CJ, et al. Potent in vitro and in vivo antitoxoplasma activity of the lipid-soluble antifolate trimetrexate. J Clin Invest. 1987 Feb;79(2):478-82.  [Content Brief]

  [4]. Dethloff LA, et al. Chronic toxicity of the anticancer agent trimetrexate in rats. Fundam Appl Toxicol. 1992 Jul;19(1):6-14.  [Content Brief]

  [5]. Grem JL, Voeller DM, Geoffroy F, Horak E, Johnston PG, Allegra CJ. Determinants of trimetrexate lethality in human colon cancer cells. Br J Cancer. 1994 Dec;70(6):1075-84.  [Content Brief]