Atovaquone是泛醌的羟基-1,4-萘醌类似物，也称为辅酶Q10（CoQ10）。
Cas No.:95233-18-4
Sample solution is provided at 25 µL, 10mM.
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Atovaquone is a hydroxy-1,4-naphthoquinone analogue of ubiquinone, also known as Co-enzyme Q10 (CoQ10)[1]. Atovaquone is thought to act as a potent and selective OXPHOS inhibitor, by targeting the CoQ10-dependence of mitochondrial complex III[1]. Atovaquone also has anti-cancer activity, directed against Cancer Stem-like Cells (CSCs)[1]. Atovaquone is an FDA-approved antimalarial drug, currently primarily used clinically to treat Pneumocystis pneumonia (PCP) and toxoplasmosis in immunocompromised patients[1].
In vitro, 5-10μM Atovaquone treatment of MCF7 breast cancer cells for 48h inhibits oxygen-consumption and metabolically induced aerobic glycolysis (the Warburg effect), as well as oxidative stress[1]. Atovaquone potently inhibited the propagation of MCF7-derived CSCs, with an IC50 of 1μM[1]. A 24h treatment with Atovaquone alleviated hypoxia in FaDu spheroids at 30μM and in HCT116 and H1299 spheroids at 20μM[2].
In vivo, oral administration of Atovaquone (50mg/kg/d) to FaDu and HCT116 xenograft mice for 7 days did not alter tumor volume but almost completely eliminated tumor hypoxia[2]. Treatment with Atovaquone (17-25mg/kg, p.o.) plus proguanil reduced parasitemia in dogs infected with Babesia gibsoni, although relapse of parasitic infection was observed[3].
References:
[1] 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.
[2] Ashton TM, Fokas E, Kunz-Schughart LA, et al. The anti-malarial atovaquone increases radiosensitivity by alleviating tumour hypoxia. Nat Commun. 2016;7:12308.
[3] Iguchi A, Matsuu A, Fujii Y, Ikadai H, Hikasa Y. The in vitro interactions and in vivo efficacy of atovaquone and proguanil against Babesia gibsoni infection in dogs. Vet Parasitol. 2013;197(3-4):527-533.
Atovaquone是泛醌的羟基-1,4-萘醌类似物，也称为辅酶Q10 （CoQ10）[1]。Atovaquone被认为是一种有效的选择性OXPHOS抑制剂，通过靶向线粒体复合体III的CoQ10依赖性来发挥作用[1]。Atovaquone还具有抗肿瘤活性，主要针对癌症干细胞样细胞（CSCs）[1]。Atovaquone是FDA批准的抗疟疾药物，目前临床上的主要用途是治疗免疫功能低下患者的肺囊虫性肺炎（PCP）和弓形虫病[1]。
体外实验中，5-10μM Atovaquone处理MCF7乳腺癌细胞48小时会抑制细胞氧消耗，并在代谢上诱导有氧糖酵解（瓦伯格效应），同时还会引起氧化应激[1]。Atovaquone能有效抑制MCF7细胞来源的癌症干细胞的增殖，其IC50值为1μM[1]。用Atovaquone处理24小时后，在30μM浓度下可缓解FaDu细胞球的缺氧状态，在20μM浓度下可缓解HCT116和H1299细胞球的缺氧状态[2]。
体内实验中，在移植了FaDu和HCT116肿瘤细胞的小鼠中，按照50mg/kg/天的剂量，连续7天口服灌胃Atovaquone，肿瘤体积不变，但肿瘤缺氧情况几乎完全消除[2]。口服Atovaquone（17-25mg/kg）和proguanil联合治疗感染Babesia gibsoni的狗，可以缓解寄生虫血症，但观察到寄生虫感染复发[3]。
| Cell experiment [1]: | |
Cell lines | MCF7 breast cancer cells |
Preparation Method | MCF7 cells were treated with Atovaquone (5μM and 10μM) for 48 hours. Vehicle alone (DMSO) control cells were processed in parallel. |
Reaction Conditions | 5μM and 10μM; 48h |
Applications | Atovaquone treatment markedly inhibited the mitochondrial respiration, with significant reductions in basal respiration, maximal respiration, and ATP levels. Atovaquone treatment increased aerobic glycolysis, glycolytic reserve, and glycolytic reserve capacity. Atovaquone treatment decreased mitochondrial mass and membrane potential, with an increase in ROS levels. |
| Animal experiment [2]: | |
Animal models | BALB/c nude female mice subcutaneously injected with FaDu or HCT116 cells |
Preparation Method | Mice bearing FaDu and HCT116 xenografts were treated with 50mg/kg Atovaquone for 7 days to investigate the effect on tumour hypoxia. Tumours were harvested after i.p. administration of 0.01ml/g of 10mM EF5 and measured with calipers after 7 days treatment. |
Dosage form | 50mg/kg/d; 7d; p.o. |
Applications | The tumour volume was not significantly altered and EF5 staining confirmed that tumour hypoxia was virtually abolished in both the FaDu and HCT116 xenografts. |
References: | |
| Cas No. | 95233-18-4 | SDF | |
| 别名 | 阿托伐醌; Atavaquone | ||
| 化学名 | 3-(4-(4-chlorophenyl)cyclohexyl)-4-hydroxynaphthalene-1,2-dione | ||
| Canonical SMILES | ClC1=C([H])C([H])=C(C([H])=C1[H])C2([H])C([H])([H])C([H])([H])C(C(C3=O)=C(C4=C([H])C([H])=C([H])C([H])=C4C3=O)O[H])([H])C([H])([H])C2([H])[H] | ||
| 分子式 | C22H19ClO3 | 分子量 | 366.84 |
| 溶解度 | ≥ 17.03mg/mL in DMSO | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.726 mL | 13.6299 mL | 27.2598 mL |
| 5 mM | 545.2 μL | 2.726 mL | 5.452 mL |
| 10 mM | 272.6 μL | 1.363 mL | 2.726 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >99.50% Appearance: A solid
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