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Tetrahydrouridine

CAS No. : 18771-50-1

MCE 站：Tetrahydrouridine

产品活性：Tetrahydrouridine dihydrate 是一种有效的胞苷脱氨酶 (CDA) 抑制剂，竞争性阻断酶的活性位点。

研究领域：Others

作用靶点：Others

In Vitro: Tetrahydrouridine (THU) is a specific inhibitor of cytidine deaminase (CDA) which can suppress deamination in the catabolism of cytotoxic deoxycytidine analogues like ara-C ａnd Gemcitabine. To test how Tetrahydrouridine affects the Gemcitabine-mediated anti-neoplastic effect on pancreatic ａnd lung carcinoma cells, a combination therapy is performed. As expected, high CDA expression in BxPC-3 ａnd H441 results in improved Gemcitabine sensitivity after a 100 M Tetrahydrouridine treatment. The sensitivity of BxPC-3 ａnd H441 cell lines increases by as much as approximately 2.1 ａnd 4.4 fold respectively. On the other hand, MIAPaCa-2 ａnd H1299 cells unexpectedly become more sensitive to Gemcitabine with low CDA expression. MIAPaCa-2 ａnd H1299 cells show a change in IC₅₀ of 2.2 ａnd 2.3 fold respectively. However, Panc-1 ａnd H322 cells do not show significant changes in drug sensitivity. These data suggested that Tetrahydrouridine can sensitize some pancreatic ａnd lung carcinoma cells to Gemcitabine-induced cell death regardless of CDA expression levels. Tetrahydrouridine inhibits S-phase without apoptosis.

In Vivo: Administration of 167 mg/kg Tetrahydrouridine (THU) followed by 1.0 mg/kg DAC results in death in one male ａnd eight females. Animals surviving to scheduled termination are generally asymptomatic with no treatment related effects observed in body weights, food consumption, clinical chemistry ａnd urinalysis for a treatment up to 1.0 mg/kg DAC in combination with 167 mg/kg Tetrahydrouridine in animals.

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