4822 T3D4767 Hydroxyurea An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. 127-07-1 3657 CH4N2O2 White powder. 133-136°C 1E+006 mg/L (at 25°C) Well absorbed from the gastrointestinal tract. Hydroxyurea is converted to a free radical nitroxide (NO) in vivo, and transported by diffusion into cells where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, inactivating the enzyme. The entire replicase complex, including ribonucleotide reductase, is inactivated and DNA synthesis is selectively inhibited, producing cell death in S phase and synchronization of the fraction of cells that survive. Repair of DNA damaged by chemicals or irradiation is also inhibited by hydroxyurea, offering potential synergy between hydroxyurea and radiation or alkylating agents. Hydroxyurea also increases the level of fetal hemoglobin, leading to a reduction in the incidence of vasoocclusive crises in sickle cell anemia. Levels of fetal hemoglobin increase in response to activation of soluble guanylyl cyclase (sGC) by hydroxyurea-derived NO. Hepatic. Route of Elimination: Renal excretion is a pathway of elimination. Half Life: 3-4 hours Oral, mouse: LD<sub>50</sub> = 7330 mg/kg; Oral, rat: LD<sub>50</sub> = 5760 mg/kg 3, not classifiable as to its carcinogenicity to humans. (L135) For management of melanoma, resistant chronic myelocytic leukemia, and recurrent, metastatic, or inoperable carcinoma of the ovary and Sickle-cell anemia. Teratogenicity: Teratogenic effects have occurred in experimental animals. Hydroxyurea use during a small number of human pregnancies has been reported. Adverse effects have not been observed in any of the exposed newborns. Reproductive Effects: Adverse reproductive effects have occurred in experimental animals. Mutagenicity: Mutagenic effects have occurred in experimental animals.Mutagenic effects have occurred in humans. 2014-09-11T05:15:44Z 2014-12-24T20:26:57Z Hydroxyurea C07044 5816 DB01005 NHY true ONC(O)=N CH4N2O2 InChI=1S/CH4N2O2/c2-1(4)3-5/h5H,(H3,2,3,4) InChIKey=VSNHCAURESNICA-UHFFFAOYSA-N 76.0547 76.027277382 Exogenous Solid -1.8 HMDB15140 CHEMBL467 3530 <p>Dee W. Brooks, Andrew O. Stewart, Richard A. Craig, &#8220;Substituted aryl- and heteroarylalkenyl-N-hydroxyurea inhibitors of leukotriene biosynthesis.&#8221; U.S. Patent US5506261, issued October, 1990.</p>