Atovaquone

产品说明书

Print
Chemical Structure| 95233-18-4 同义名 : Atavaquone; BW 566C; Wellvone; Mepron; hydroxynaphthoquinone 566C80; GlaxoSmithKline brand of atovaquone; Glaxo Wellcome brand of atovaquone; compound 566; atovaquone GlaxoSmithKline brand; 566C80 hydroxynaphthoquinone; 566C80; 566C; BW 556C-80
CAS号 : 95233-18-4
货号 : A242112
分子式 : C22H19ClO3
纯度 : 99%
分子量 : 366.84
MDL号 : MFCD00889188
存储条件：

Pure form Sealed in dry, store in freezer, under -20°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 : -
动物实验配方：

5% DMSO+corn oil 0.5 mg/mL

生物活性
描述 Atovaquone is a powerful suppressor of protozoan parasites with a broad-spectrum activity, but an extremely low water solubility and bioavailability. Oral administration of atovaquone nanoemulsion increased oral bioavailability, tissue distribution and mice survival time and reduced parasitemia and number and size of the brain cysts[3]. While atovaquone has potent in vitro activity against Toxoplasma gondii, it is poorly absorbed after oral administration and shows poor therapeutic efficacy against TE(toxoplasma encephalitis). Development of TE and mortality in mice treated with 1.0- or 0.1-mg/kg i.v. doses of ANS (atovaquone nanosuspensions) did not differ from that in mice treated orally with 100 mg of atovaquone/kg[4]. Atovaquone, an antiprotozoal and antipneumocystic agent, is predominantly cleared by biliary excretion of unchanged parent drug[5]. Atovaquone potently inhibits the propagation of MCF7-derived CSCs, with an IC-50 of 1 μM, as measured using the mammosphere assay. In addition to targeting the proliferation of CSCs (Cancer Stem-like Cells), atovaquone also induces apoptosis in both CD44+/CD24low/- CSC and ALDH+ CSC populations, during exposure to anchorage-independent conditions for 12 hours[6].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT03163121 Malaria Phase 1 Recruiting October 2018 Netherlands ... 展开 >> Leiden University Medical Center, Albinusdreef 2 Recruiting Leiden, Netherlands, 2333 ZA Contact: Leo G. Visser, MD    31715266354    l.g.visser@lumc.nl    Contact: Meta Roestenberg, MD, PhD    31715264400    M.Roestenberg@lumc.nl    Principal Investigator: Leo G. Visser, MD          Radboud University Medical Center, Geert Grooteplein 28 Recruiting Nijmegen, Netherlands, 6525 GA Contact: Robert W. Sauerwein, MD    31243610577    Robert.Sauerwein@radboudumc.nl    Contact: Jona Walk, MD    31243613663    Jona.Walk@radboudumc.nl    Principal Investigator: Robert W. Sauerwein, MD 收起 <<
NCT01218893 Plasmodium Falciparum Malaria Not Applicable Completed - Netherlands ... 展开 >> Leiden University Medical Centre Leiden, Netherlands, 2300 RC 收起 <<
NCT01236612 Plasmodium Falciparum Malaria Not Applicable Completed - Netherlands ... 展开 >> Radboud University Nijmegen Medical Centre Nijmegen, Netherlands, 6500 HB 收起 <<
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.73mL

0.55mL

0.27mL

13.63mL

2.73mL

1.36mL

27.26mL

5.45mL

2.73mL
参考文献

[1]Kessl JJ, Lange BB, et al. Molecular basis for atovaquone binding to the cytochrome bc1 complex. J Biol Chem. 2003 Aug 15;278(33):31312-8.

[2]Looareesuwan S, Viravan C, et al. Clinical studies of atovaquone, alone or in combination with other antimalarial drugs, for treatment of acute uncomplicated malaria in Thailand. Am J Trop Med Hyg. 1996 Jan;54(1):62-6.

[3]Azami SJ, Amani A, Keshavarz H, et al. Nanoemulsion of atovaquone as a promising approach for treatment of acute and chronic toxoplasmosis. Eur J Pharm Sci. 2018;117:138‐146

[4]Schöler N, Krause K, Kayser O, et al. Atovaquone nanosuspensions show excellent therapeutic effect in a new murine model of reactivated toxoplasmosis. Antimicrob Agents Chemother. 2001;45(6):1771‐1779

[5]Patel M, Johnson M, Sychterz CJ, et al. Hepatobiliary Disposition of Atovaquone: A Case of Mechanistically Unusual Biliary Clearance. J Pharmacol Exp Ther. 2018;366(1):37‐45

[6]Fiorillo M, Lamb R, Tanowitz HB, et al. Repurposing atovaquone: targeting mitochondrial complex III and OXPHOS to eradicate cancer stem cells. Oncotarget. 2016;7(23):34084‐34099