Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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In Vivo Antitumor Efficacy of Cw252053, A Folate-based Thymidylate Synthase Inhibitor

  • Oh, Se-Woong (Research Laboratory, R＆D Division, Choongwae Pharma Co.,) ;
  • Ha, Jong-Ryul (Research Laboratory, R＆D Division, Choongwae Pharma Co.,) ;
  • Baek, Du-Jong (Research Laboratory, R＆D Division, Choongwae Pharma Co., and Department of Chemistry, College of Natural Science, Sangmyung University)
  • Published : 2001.08.01
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Abstract

Previous studies have demonstrated that CW252053, a quinazoline antifolate, exhibits potent inhibitory activity against thymidylate synthase (TS) as well as cytotoxic activity against tumor cell lines in vitro. In this studys, we evaluated the in vivo antitumor efficacy of CW252053 in the mouse tumor model. Female B6D2F$_1$ mice were injected with LY3.7. 2C TK-/- (thymidine kinase deficient mouse Iymphoma) cells into the gastrocnemius muscle. Then, CW252053 was administered twice daily by intraperitoneal injection for 10 days, and tumor growth was monitored daily by leg diameter measurement. All animals in the vehicle, 5-FU, and low dose (30mgmg/kg CW252053 treated groups died between days 12 and 23 because of the tumor burden. In contrast, dosing with 60 mg/kg of CW252053 produced a cure rat against tumor growth of 37.5% and a survival rate of 50%. Even more significantly, a higher dose of CW252053 (120 mg/kg) elicited both a 100% cure rate and a 100% survival rate at the termination of the study, confirming that this compound has very potent in vivo antitumor activity against tumor growth. During the experimental period of this study no signs of toxicity were observed even at the high CW252053 dosage rate of 120 mg/kg.

Keywords

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