Visomitin (SKQ-1)

Mitochondrial-targeting antioxidant

对肿瘤浸润白细胞施用 Visomitin (SkQ1) 不会影响其对 Panc02 细胞的细胞毒性。在 500 nM 浓度下，visomitin 显着抑制人 PDAC 细胞的生长，同时对细胞系的活力没有影响[1]。

就全身血管生成因子而言，在接受 Viomitin (SkQ1) 连续治疗的胰腺导管腺癌 (PDAC) 小鼠血清中，KC 较低。 Visomitin 治疗可增加小鼠体内 VEGF 分子的数量。后续治疗后或所有 Visomitin 治疗组中催乳素和 MIP1a 水平分别降低。此外，接受维索丁治疗的组中 IL-6 和 IL-13 水平较高。预处理设置会导致 TGF-b 水平降低。相反，每个 Visomitin 治疗计划都会降低 NKT 细胞的百分比。使用 Visomitin 治疗后，携带 PDAC 的小鼠的中位生存期有所增加，但这种变化并不具有统计学意义[1]。

用不同浓度的 Visomitin (SkQ1) 处理 Panc02 细胞 48 小时。按照制造商的说明，使用 EZ4U 试剂盒测量 Visomitin 处理后的细胞活力。简而言之，将每孔 20,000 个细胞接种到 96 孔板中并生长过夜。然后，在不更换培养基的情况下处理细胞。添加试剂盒中的底物化合物，并将细胞在 37°C 下进一步孵育 5 小时，以通过活细胞将黄色四唑转化为其红色甲臜衍生物。吸光度在 450 nm 处测量[1]。

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根据制造商的说明，用溴脱氧尿苷（BrdU）细胞增殖测定试剂盒分析细胞系的增殖。简而言之，将20000个细胞接种在96孔板中，并让其生长过夜。用SKQ孵育后，加入BrdU试剂，并在37°C下进一步孵育细胞12小时，以使BrdU掺入增殖细胞。然后，固定细胞，洗涤，并加入检测抗体。将板在室温下孵育1小时并洗涤。加入试剂盒中的山羊抗小鼠IgG-过氧化物酶偶联物，并在室温下孵育平板30分钟。进一步洗涤后，将细胞在室温下与3,3′，5,5′-四甲基联苯胺过氧化物酶底物在黑暗中孵育30分钟。通过加入试剂盒中的酸终止溶液来停止反应。在450nm处测量吸光度。[1]

SkQ1 treatment of mice[1]
Drinking water for C57BL/6 mice was supplemented with SkQ1 to yield a dose of 5 nmol SkQ1/kg body weight per day (on average, a mouse drank about 5 mL of water per day).12 The following experimental groups have been used: (1) control group (no SkQ1 in drinking water); (2) pretreatment group (animals treated with SkQ1 3 weeks before operation, no SkQ1 after Panc02 cell injection); (3) treatment group (animals received SkQ1 only after operation, without pretreatment); and (4) continuous treated group consisted of mice treated with SkQ1 both before and after tumor cell transplantation.

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For experiments on chronic pancreatitis, mice received cerulein (50 μg/kg/injection in saline) or saline (control) at five hourly injections of cerulein three times a week over a period of eight weeks. Antioxidative treatment with SkQ1 (10-(6′-plastoquinonyl)decyltriphenylphosphonium) was administered perorally with the drinking water at a dose of 5 nmol/kg body weight per day (on average, a mouse drank about 5 mL of water per day).[2]

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For experiments on both acute and chronic pancreatitis, mice were divided in three groups. Group A (acute pancreatitis (AP) n = 8; chronic pancreatitis (CP) n = 12) was treated with 5 nmol/kg SkQ1, group B (AP n = 8; CP n = 12) was the untreated control, and group C (AP n = 8; CP n = 7) was the sham group, which was injected intraperitoneally with 0.9% NaCl instead of cerulein and was therefore the negative control group without pancreatitis.[2]

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For experiments on acute pancreatitis, mice were pretreated with SkQ1 for 8 weeks prior to induction of pancreatitis. Mice designated for experiments on chronic pancreatitis received SkQ1 at the same concentration for 8 weeks in parallel with induction of pancreatitis.[2]

[1]. The novel mitochondria-targeted antioxidant SkQ1 modulates angiogenesis and inflammatory micromilieu in a murine orthotopic model of pancreatic cancer. Int J Cancer. 2016 Jul 1;139(1):130-9.

[2]. The Analgesic Effect of the Mitochondria-Targeted Antioxidant SkQ1 in Pancreatic Inflammation. Oxid Med Cell Longev. 2016;2016:4650489.

Our understanding in the last few years about reactive oxygen species (ROS) has changed from being harmful substances to crucial intra- and extracellular messengers as well as important regulators controlling a wide spectrum of signaling pathways, including those in cancer immunology. Therefore, these multiple essential roles of ROS and especially of mitochondria-derived ROS in malignant transformation and cancer progression make them a promising target for anticancer therapy. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the world. A link between ROS, antioxidants and the PDAC development and progression has been recently established. Therefore, usage of specific highly efficient antioxidants could bring an option for treatment and/or prevention of PDAC. 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) is a new antioxidant with the highest mitochondrion membrane penetrating ability and potent antioxidant capability. In this work, we investigated an impact of SkQ1 on tumor angiogenesis, immune micromilieu, and oncological parameters in the orthotopic Panc02 murine model of PDAC. We showed that in this model SkQ1 treatment leads to the elevation of pro-angiogenic factors and to building of mainly an anti-inflammatory cytokine milieu. On the cellular level we showed an increase in a percentage of memory T cells and a decrease in frequency on natural killer T (NKT) cells. At the same time, SkQ1 was ineffective in the improvement of oncological parameters of PDAC-bearing mice. New studies are needed to clarify the absence of therapeutic and/or prophylactic benefits of the antioxidant.[1]

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Background. Chronic pancreatitis is one of the main risk factors for pancreatic cancer. In acute and chronic pancreatitis, oxidative stress is thought to play a key role. In this respect, the recently described mitochondria-targeted antioxidant SkQ1 effectively scavenges reactive oxygen species at nanomolar concentrations. Therefore, we aimed to characterize the influence of SkQ1 on tissue injury and pain in acute and chronic pancreatitis. Methods. Both acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal cerulein injections and treatment with SkQ1 was carried out by peroral applications. Hyperalgesia was assessed by behavioral observation and measurement of abdominal mechanical sensitivity. Blood serum and pancreatic tissue were harvested for analysis of lipase and histology. Results. SkQ1 did not influence pain, serological, or histological parameters of tissue injury in acute pancreatitis. In chronic pancreatitis, a highly significant reduction of pain-related behavior (p < 0.0001) was evident, but histological grading revealed increased tissue injury in SkQ1-treated animals (p = 0.03). Conclusion. After SkQ1 treatment, tissue injury is not ameliorated in acute pancreatitis and increased in chronic pancreatitis. However, we show an analgesic effect in chronic pancreatitis. Further studies will need to elucidate the risks and benefits of mitochondria-targeted antioxidants as an analgesic.[2]

C36H42BRO2P

617.61

616.21

C, 70.01; H, 6.85; Br, 12.94; O, 5.18; P, 5.02

934826-68-3

934826-68-3 (bromide);934960-96-0 (cation);1372443-45-2 (chloride);1372443-48-5 (sulfate); 714085-40-1 (iodide);

16679091

Yellow to brown solid powder

8.864

47.73

0

3

14

40

804

0

WYHFWTRUGAFNKW-UHFFFAOYSA-M

InChI=1S/C36H42O2P.BrH/c1-29-30(2)36(38)31(28-35(29)37)20-12-7-5-3-4-6-8-19-27-39(32-21-13-9-14-22-32,33-23-15-10-16-24-33)34-25-17-11-18-26-34/h9-11,13-18,21-26,28H,3-8,12,19-20,27H2,1-2H31H/q+1/p-1

(10-(4,5-dimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)decyl)triphenylphosphonium bromide

SKQ1; SKQ-1; SKQ 1; 934826-68-3; SKQ1 bromide; SKQ-1 bromide; SKQ1; 934826-68-3 (bromide); (10-(4,5-dimethyl-3,6-dioxocyclohexa-1,4-dien-1-yl)decyl)triphenylphosphonium bromide; 7B14500J3E; PDTP; Plastoquinonyl decyltriphenyl phosphonium bromide; Visomitin

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

注意： 请将本产品存放在密封且受保护的环境中（例如氮气保护），避免吸湿/受潮。

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~161.92 mM)
Ethanol : ~50 mg/mL (~80.96 mM)
H2O : ~3.33 mg/mL (~5.39 mM)

配方 1 中的溶解度: ≥ 2.5 mg/mL (4.05 mM) (饱和度未知) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加), 澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL澄清DMSO储备液加入到400 μL PEG300中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 2 中的溶解度: 2.5 mg/mL (4.05 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加), 悬浊液; 超声助溶。
例如，若需制备1 mL的工作液，可将 100 μL 25.0 mg/mL澄清DMSO储备液加入900 μL 20% SBE-β-CD生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 3 中的溶解度: ≥ 2.5 mg/mL (4.05 mM) (饱和度未知) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (这些助溶剂从左到右依次添加，逐一添加),澄清溶液。
例如，若需制备1 mL的工作液，将 100 μL 25.0 mg/mL 澄清乙醇储备液加入到 400 μL PEG300 中，混匀；然后向上述溶液中加入50 μL Tween-80，混匀；加入450 μL生理盐水定容至1 mL。
*生理盐水的制备：将 0.9 g 氯化钠溶解在 100 mL ddH₂O中，得到澄清溶液。

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配方 4 中的溶解度: ≥ 2.5 mg/mL (4.05 mM) (饱和度未知) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (这些助溶剂从左到右依次添加，逐一添加),澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL 澄清乙醇储备液加入到 900 μL 20% SBE-β-CD 生理盐水溶液中，混匀。
*20% SBE-β-CD 生理盐水溶液的制备（4°C，1 周）：将 2 g SBE-β-CD 溶解于 10 mL 生理盐水中，得到澄清溶液。

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配方 5 中的溶解度: ≥ 2.5 mg/mL (4.05 mM) (饱和度未知) in 10% EtOH + 90% Corn Oil (这些助溶剂从左到右依次添加，逐一添加),澄清溶液。
例如，若需制备1 mL的工作液，可将100 μL 25.0 mg/mL 澄清 EtOH 储备液加入900 μL 玉米油中，混合均匀。

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请根据您的实验动物和给药方式选择适当的溶解配方/方案：
1、请先配制澄清的储备液(如：用DMSO配置50 或 100 mg/mL母液(储备液));
2、取适量母液，按从左到右的顺序依次添加助溶剂，澄清后再加入下一助溶剂。以 下列配方为例说明 (注意此配方只用于说明，并不一定代表此产品 的实际溶解配方):
10% DMSO → 40% PEG300 → 5% Tween-80 → 45% ddH2O (或 saline);
假设最终工作液的体积为 1 mL, 浓度为5 mg/mL: 取 100 μL 50 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀/澄清；向上述体系中加入50 μL Tween-80，混合均匀/澄清；然后继续加入450 μL ddH2O (或 saline)定容至 1 mL；
3、溶剂前显示的百分比是指该溶剂在最终溶液/工作液中的体积所占比例;
4、 如产品在配制过程中出现沉淀/析出，可通过加热(≤50℃)或超声的方式助溶;
5、为保证最佳实验结果，工作液请现配现用！
6、如不确定怎么将母液配置成体内动物实验的工作液，请查看说明书或联系我们;
7、 以上所有助溶剂都可在 Invivochem.cn网站购买。