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Nagourney, R.A. et al.

A comparison of the biological and biochemical properties of 1-(4-amino-2-methylpyrimidin-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea and 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose.

1-4-Amino-2-methylpyrimidin-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) is a water-soluble nitrosourea that has produced delayed hematological toxicity in man during Phase 1 clinical trials. ACNU has in vitro alkylating activy 40% less than that of 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose (chlorozotocin) but shares the property of negligible carbamoylating activity with the latter compounds. ACNU is highly active against murine L1210 leukemia. However, the maximum therapeutic dose, 30 mg/kg (a dose lethal to 10% of the animals), produced a 64% reduction in peripheral WBC and an 85% decrease in circulating neutrophils in normal mice. This was correlated with a 76% inhibition of normal mouse bone marrow DNA synthesis within 24 hr after treatment, followed by full recovery within 48 hr after treatment, followed by full recovery within 48 hr. In contrast, DNA synthesis in L1210 cells was suppressed to less than 10% of control for a minimum of 72 hr. While ACNU, a pyrimidine analog, possesses many of the chemical properties of chlorozotocin, it does not share with the latter compound its reduced myelotoxicity at therapeutic doses. The glucose carrier of the chlorozotocin molecule appears to impart the selective sparing of normal bone marrow.[1]

References

A comparison of the biological and biochemical properties of 1-(4-amino-2-methylpyrimidin-5-yl)methyl-3-(2-chloroethyl)-3-nitrosourea and 2-[3-(2-chloroethyl)-3-nitrosoureido]-D-glucopyranose. Nagourney, R.A., Fox, P., Schein, P.S. Cancer Res. (1978) [Pubmed]

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