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Chemical Compound Review:

trimetrexate 5-methyl-6-[[(3,4,5- trimethoxyphenyl)amino...

Synonyms: Trimetrexato, Trimetrexatum, Jb-11, CI-898, NSC-249008, ...

Mayer-Kuckuk, P. et al., Harris, P.J., Hook, K.E. et al.

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Disease relevance of trimetrexate

Next, human HCT-8 and HCT-116 colon cancer cells retrovirally transduced to express a DHFR-herpes simplex virus 1 thymidine kinase (HSV1 TK) fusion protein and treated with the DHFR inhibitor TMTX exhibited increased levels of the DHFR-HSV1 TK fusion protein and an increase in ganciclovir sensitivity by 250-fold [1].

High impact information on trimetrexate

Cell cycle effects of trimetrexate (CI-898) [2].
This is a report on a patient with AIDS who developed Pneumocystis carinii pneumonia, which was treated with trimethoprim sulfamethoxazole (Bactrim) with poor response, then with pentamidine with poor response, and finally with trimetrexate glucuronate (Neutrexin) and leucovorin rescue, with good response [3].

Analytical, diagnostic and therapeutic context of trimetrexate

In a xenograft model, nude rats bearing DHFR-HSV1 TK-transduced HCT-8 tumors and treated with TMTX showed, after 24 h, a 2- to 4-fold increase of fusion-protein levels in tumor tissue from treated animals compared with controls, as determined by Western blotting [1].

References

Cells exposed to antifolates show increased cellular levels of proteins fused to dihydrofolate reductase: a method to modulate gene expression. Mayer-Kuckuk, P., Banerjee, D., Malhotra, S., Doubrovin, M., Iwamoto, M., Akhurst, T., Balatoni, J., Bornmann, W., Finn, R., Larson, S., Fong, Y., Gelovani Tjuvajev, J., Blasberg, R., Bertino, J.R. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
Cell cycle effects of trimetrexate (CI-898). Hook, K.E., Nelson, J.M., Roberts, B.J., Griswold, D.P., Leopold, W.R. Cancer Chemother. Pharmacol. (1986) [Pubmed]
Trimetrexate glucuronate associated with anti-Kaposi sarcoma effect. Harris, P.J. AIDS patient care and STDs. (1996) [Pubmed]

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