Detail of "152946-68-4"

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Synergy between the non-classical thymidylate synthase inhibitor AG337 (Thymitaq) and cisplatin in human colon and ovarian cancer cells

Synergy between the non-classical thymidylate synthase inhibitor AG337 (Thymitaq) and cisplatin in human colon and ovarian cancer cells. Raymond, Eric; Djelloul, Siham; Buquet-Fagot, Christine; Mester, Jan; Gespach, Christian (Inst. Federatif de recherches du Centre Hospitalo, Univ. Paris Saint-Antoine, Paris 75571, Fr.). Anti-Cancer Drugs, 7(7), 752-757 (English) 1996 Rapid Science Publishers. CODEN: ANTDEV. ISSN: 0959-4973. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) AG337 is a recent non-classical thymidylate synthase inhibitor with promising activity and manageable toxicity in phase I clin.There are some reagents with their cas registry numbers 15663-27-1 and 152946-68-4 are used in this study. trials. In this study, we investigated the cytotoxic activity of AG337 alone and in combination with cisplatin in cultured human colon (HT29) and ovarian (2008) cancer cell lines and their derived counterparts selected for this resistance to 5-fluorouracil (5-FU) (HT29-5-FU) and cisplatin (2008C13). We obsd. that AG337 had potent cytotoxic effects in color (IC50 = 0.17 mM) and ovarian cancer cells (IC50 = 0.65 mM). The cytotoxic activity of AG337 was higher than that of 5-FU in the two models. The activity of AG337 was not significantly affected in 5-FU-resistant HT29-5-FU colon cancer cells characterized by an amplification of the thymidylate synthase gene (IC50 = 0.27 mM, p = 0.15). Combinations of cisplatin and AG337 exert synergistic activity in both ovarian and colon cancer cells. Interestingly, this synergism was maintained in 5-FU- and cisplatin-resistant cells. Therefore, our data encourage further examn. of combinations of AG337 with cisplatin in cancer chemotherapy. .

Phase II trial of nolatrexed dihydrochloride [Thymitaq, AG 337] in patients with advanced hepatocellular carcinoma

All Rights Reserved. Phase II trial of nolatrexed dihydrochloride [Thymitaq, AG 337] in patients with advanced hepatocellular carcinoma. Jhawer, Minaxi; Rosen, Lee; Dancey, Janet; Hochster, Howard; Hamburg, Solomon; Tempero, Margaret; Clendeninn, Neil; Mani, Sridhar (Montefiore Medical Center, New York, NY, USA). Investigational New Drugs, Volume Date 2007, 25(1), 85-94 (English) 2006 Springer. CODEN: INNDDK. ISSN: 0167-6997. DOCUMENT TYPE: Journal CA Section: 1 (Pharmacology) Background: To evaluate the tolerability and efficacy of nolatrexed in patients with advanced hepatocellular carcinoma. Patients and methods: Forty-eight patients were entered onto this study. Nolatrexed was administered every 3 wk as a 24-h continuous i.v. infusion of 725 mg/m2/day for 5 days. Doses were adjusted to maintain a dose level that produced grade 2 toxicity. Response was assessed after every two cycles. Plasma pharmacokinetic samples were assayed using a validated high performance liq. chromatog.Several reagents such as 152946-68-4 is used here. UV method. Results: Thirty-nine (81%) patients were evaluable for response. The mean no. of cycles received was 2.8 (range 1-12). The mean dose intensity was 700 mg/m2/day (SD of 71). One patient had a partial response (2.6%) for 7 mo. Eighteen (46%) patients had SD, 20 (51%) patients had progressive disease. The median duration of SD was 93 days. The median overall survival was 32 wk [95% CI (22-37)]. The most frequent Grade 3 or 4 adverse events were stomatitis (25%), dehydration (23%) and asthenia (21%). There was no evidence of cumulative toxicity. The overall median plasma concn. (Cmax) was 14.20 mg/mL (range 1.41 to 119 mg /mL) with no accumulation obsd. between cycles 1-6. Conclusion: This phase II study of nolatrexed in advanced HCC patients, demonstrated minimal activity and significant stomatitis. Hence, it does not warrant further study as a single agent for this disease. .