Disease relevance of AIDS045503

• Thirty-three patients with advanced measurable gastric cancer were treated with a combination of mitomycin C and triazinate [1].
• When triazinate was given by a multiple-dose schedule every 12 to 24 hr, there was no neurological toxicity, but mucositis, skin toxicity, and myelotoxicity were increased [2].
• The incidence of dermatitis was significantly decreased by shortening the schedule of Baker's Antifol administration from 5 to 3 days [3].
• Twenty-nine patients with advanced ovarian carcinoma were entered into a Gynecologic Group Phase II study of Baker's Antifol [4].
• The drug combinations of dianhydrogalactitol and VP-16 and dianhydrogalactitol, VP-16, and triazinate were used in patients with primary brain tumors, principally astrocytoma, recurrent following cranial irradiation [5].

High impact information on AIDS045503

• A series of increasingly drug-resistant cell populations were selected and cloned from C-46 murine neuroblastoma with the chemotherapeutic drugs maytansine, vincristine, adriamycin, or Baker's antifol [6].
• ABCB1 expression correlated negatively with potencies of 19 known ABCB1 substrates and with Baker's antifol and geldanamycin [7].
• Triazinate, at 10(-3) M, had no significant effect on thymidylate synthetase activity [8].
• Twenty-four patients with advanced solid tumors and seven with acute leukemia were treated with a triazine folate antagonist, triazinate, to determine the toxicity spectrum, the maximum tolerated dose, and the pharmacological disposition of the drug [2].
• Methotrexate-dimethylester, methasquin-diethylester, DDEP (2,4-diamino-5-(3',4'-dichlorophenyl)-6-ethylprimidine), and Baker's triazine antifolate (NSC 139105), while less effective than MTX as DHFR inhibitors, were more effective than MTX as inhibitors of de novo DNA synthesis in rat skin in vitro [9].

Chemical compound and disease context of AIDS045503

• The drug triazinate appears to have activity in gastric cancer, and in combination with mitomycin C produces a 28% response rate in patients who had failed chemotherapy regimens containing fluorinated pyrimidine [10].
• Cutaneous hyperpigmentation resembling acanthosis nigricans developed in two patients with malignant brain tumors following chemotherapy with triazinate (Baker's Antifol), a folic acid antagonist [11].
• However, the experience with triazinate (Baker's antifol; TZT) indicates that transport of antifols could be exploited to provide selective toxicity, as well as to provide agents effective vs. MTX-resistant cells [12].
• It is unlikely that triazinate and ICRF-159 will add substantially to the efficacy of chemotherapy for colorectal cancer [13].
• Carmustine and Baker's antifol combination chemotherapy for primary brain tumors progressive after irradiation and chemotherapy [14].

Biological context of AIDS045503

• In vivo pharmacokinetics of triazinate in L-1210 and W-256 cells [15].
• Stereochemistry of dihydrofolate reductase inhibitor antitumor agents: molecular structure of "Baker's antifol" (NSC 139105, triazinate) and "insoluble Baker's antifol" (NSC 113423) [16].
• Phase I studies were conducted in 58 adult cancer patients with Baker's Antifol (BAF), a new active-site directed inhibitor of dihydrofolate reductase [17].
• The IC50 (amount of inhibitor required for 50% loss of enzyme activity) values were 0.2 nM for MTX and aminopterin and 50 and 67 nM, respectively, for N10-formyl FA and triazinate (NSC-139105) [18].

Anatomical context of AIDS045503

• Central nervous system pharmacology of Baker's antifolate (NSC139105) in man [19].
• DNA synthesis in beagle bone marrow cells was depressed significantly by triazinate as compared with cells from rhesus marrow [20].
• Phase II study of Baker's antifol (triazinate, TZT, NSC-139,105) in advanced squamous cell carcinoma of cervix [21].

Gene context of AIDS045503

• Those with abnormal kidney or liver function were randomized between FMI and FMV because triazinate depends on both hepatic and renal mechanisms for elimination [22].

Analytical, diagnostic and therapeutic context of AIDS045503

• Baker's antifol has only limited activity against ovarian carcinoma previously treated with chemotherapy and is not likely to contribute to improved therapy, either as a single agent or in combination [4].
• Comparative distribution of Baker's antifolate (NSC 139105) in rat tissues after subcutaneous and intravenous injections [23].

References