• 生物活性

靶点及简介 ：DNA synthesis inhibitor

Hydroxyurea (NSC-32065, NCI-C04831, Hydroxycarbamide)是一种抗肿瘤药，通过抑制核苷二磷酸还原酶 ribonucleoside diphosphate reductase 而抑制DNA合成。 Hydroxyurea 可激活凋亡和自噬，并可用于治疗HIV感染。

Hydroxyurea (NSC-32065) is an antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. 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.

体外研究：

    羟基脲被用于许多骨髓增生，肿瘤，HIV和非血液疾病[1]。用30μM羟基脲处理原代培养物中的细胞96小时显着增加了HbF分数。 Gγ：Aγ-珠蛋白mRNA在体外诱导0.30至8倍[2]。羟基脲已被证明可阻断静息外周血单核细胞和巨噬细胞中的HIV-1逆转录和/或复制[3]。

体内研究

    羟基脲治疗可在17周内持续减少WBC和ANC，并且不会改善贫血。与媒介物治疗的镰状细胞小鼠相比，50mg / kg的羟基脲可以减少白细胞计数，绝对中性粒细胞计数并且贫血没有改善[4]。

动物实验

    小鼠：确定羟基脲是否能改善贫血和/或预防或减少在没有HbF诱导的情况下器官损伤的发展，羟基脲，剂量为25 mg / kg，50 mg / kg和100 mg / kg，或载体每周给予SCD小鼠5天[4]。

• 验证及参考文献

验证：

参考文献：

[1]. Kovacic P, et al. Hydroxyurea (therapeutics and mechanism): metabolism, carbamoyl nitroso, nitroxyl, radicals, cell signaling and clinical applications. Med Hypotheses. 2011 Jan;76(1):24-31.

[2]. Watanapokasin Y, et al. In vivo and in vitro studies of fetal hemoglobin induction by hydroxyurea in beta-thalassemia/hemoglobin E patients. Exp Hematol. 2005 Dec;33(12):1486-92.

[3]. Lori F, et al. Rationale for the use of hydroxyurea as an anti-human immunodeficiency virus drug. Clin Infect Dis. 2000 Jun;30 Suppl 2:S193-7.

[4]. Lebensburger JD, et al. Hydroxyurea therapy requires HbF induction for clinical benefit in a sickle cell mouse model. Haematologica. 2010 Sep;95(9):1599-603.

• 溶解度及制备方案

DMSO	15 mg/mL  (197.24 mM)
Water	15 mg/mL  (197.24 mM)
Ethanol	Insoluble

• 制备储备液

浓度   溶剂体积     质量	1 mg	5 mg	10 mg
1 mM	13.1492 mL	65.7462 mL	131.4924 mL
5 mM	2.6298 mL	13.1492 mL	26.2985 mL
10 mM	1.3149 mL	6.5746 mL	13.1492 mL
50 mM	0.2630 mL	1.3149 mL	2.6298 mL

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