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 study, we evaluated the in vivo antitumor efficacy of
CW252053 in the mouse
tumor model. Female B6D2F1 mice were injected with LY3.7.2C TK-/- (
thymidine kinase deficient mouse
lymphoma) 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 (30 mg/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 rate 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.