Mitochondrial-targeting antioxidant
Visomitin targets mitochondria, where it accumulates due to its lipophilic cation and penetrating ability. It acts as a potent antioxidant by inhibiting cardiolipin peroxidation, a key event in mitochondrial dysfunction. By reducing oxidative stress in mitochondria, it decreases the transmembrane potential and production of reactive oxygen species (ROS). This mechanism helps protect cells from mitochondrial damage and apoptosis.

Visomitin (SkQ1) administration of tumor-infiltrating leukocytes does not affect their cytotoxicity against Panc02 cells. At 500 nM concentration, visomitin significantly inhibits the growth of human PDAC cells while having no effect on the viability of the cell lines[1].
In vitro, Visomitin is a potent antioxidant that decreases transmembrane potential and ROS production in mitochondria. It has been shown to prevent neuronal loss and synaptic damage in a rat model of spontaneous Alzheimer's disease. Direct treatment of tumor infiltrating leukocytes with Visomitin does not influence their cytotoxicity against Panc02 cells.

In reference to systemic angiogenic factors, KC is shown to be lower in the group receiving continuous therapy with visomitin (SkQ1) in the serum of mice having pancreatic ductal adenocarcinoma (PDAC). Visomitin treatment raises the quantity of VEGF molecules in the mice. Prolactin and MIP1a levels are lowered following the follow-up treatment or in all Visomitin treatment groups, respectively. Furthermore, IL-6 and IL-13 levels are higher in the groups that received visomitin treatment. The pretreatment setting results in a decrease in TGF-b levels. Conversely, every Visomitin treatment plan reduces the percentage of NKT cells. The PDAC-bearing mice's median survival has increased with Visomitin treatment, however the change is not statistically significant[1].
In vivo, Visomitin has shown promise in clinical trials for the treatment of various eye disorders, including dry eye, glaucoma, and ocular inflammation. It slows the development of age-related diseases and prevents neuronal loss in animal models of Alzheimer's disease. Its potent antioxidant activity and mitochondrial targeting make it a potential therapeutic agent for diseases involving oxidative stress.

In vitro assays for Visomitin typically measure its antioxidant activity using standard methods such as the DPPH (2,2-diphenyl-1-picrylhydrazyl) assay or by assessing its ability to inhibit lipid peroxidation. Its effects on mitochondrial membrane potential and ROS production are also measured using fluorescent probes. These assays are used to quantify the compound's potency as an antioxidant.

Panc02 cells are treated 48 h with different concentrations of Visomitin (SkQ1). Cell viability after Visomitin treatment is measured with an EZ4U Kit as described by the manufacturers. Briefly, 20,000 cells per well are seeded in 96-wellplates and let grow overnight. Afterwards, cells are treated without the medium exchange. A substrate compound from the kit is added and the cells are further incubated for 5 hr at 37°C to convert the yellow colored tetrazolium to its red formazan derivate by living cells. The absorbance is measured at 450 nm[1].

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Proliferation of cell lines was analyzed with a Bromodeoxyuridine (BrdU) Cell Proliferation Assay kit according manufacturer instructions. Briefly, 20,000 cells were seeded in 96-well plates and let grow overnight. After incubation with SKQ, the BrdU reagent was added, and the cells were incubated further for 12 hr at 37°C to allow the BrdU incorporation into proliferating cells. Afterwards, the cells were fixed, washed, and a detector antibody was added. The plates were incubated for 1 hrs at room temperature and washed. A goat anti-mouse IgG peroxidase conjugate from the kit was added, and the plates were incubated for 30 min at room temperature. After further washing, the cells were incubated for 30 min at room temperature in the dark with the 3,3′,5,5′-tetramethylbenzidine peroxidase substrate. The reaction was stopped by adding the acid stop solution from the kit. The absorbance was measured at 450 nm.[1]
Cell-based assays for Visomitin involve treating cells with the compound and measuring its effects on mitochondrial function, ROS levels, and cell viability. The compound's ability to protect cells from oxidative stress-induced damage is assessed. These studies help elucidate its mechanism of action and its potential therapeutic applications.

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]
In vivo animal studies for Visomitin are conducted in models of various diseases, including Alzheimer's disease and eye disorders. The compound is administered topically or systemically, and its effects on disease progression, oxidative stress markers, and tissue damage are assessed. Clinical trials are also being conducted to evaluate its efficacy in humans.

Visomitin has a molecular weight of 617.61 g/mol and a molecular formula of C36H42BrO2P. It is a thick orange oil/gum that is very hygroscopic. The compound should be stored as supplied at -20°C for up to 1 year from the date of purchase.

The toxicological profile of Visomitin has been evaluated in preclinical and clinical studies. The compound is generally well-tolerated. As a potent antioxidant, it has a favorable safety profile. However, appropriate safety precautions should be taken when handling the compound.

[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.

In recent years, our understanding of reactive oxygen species (ROS) has shifted from harmful substances to important intracellular and extracellular messengers and key regulators of various signaling pathways, including cancer immune pathways. Therefore, the multiple important roles of ROS, especially mitochondrial-derived ROS, in malignant transformation and cancer progression make them highly promising targets for anticancer therapy. Pancreatic ductal adenocarcinoma (PDAC) is one of the world's deadliest cancers. Recent studies have confirmed the close relationship between ROS, antioxidants, and the development and progression of PDAC. Therefore, the use of highly effective and specific antioxidants holds promise for providing new options for the treatment and/or prevention of PDAC. 10-(6'-plastoquinone)decyltriphenylphosphine (SkQ1) is a novel antioxidant with extremely high mitochondrial membrane penetration and potent antioxidant activity. This study investigated the effects of SkQ1 on tumor angiogenesis, immune microenvironment, and oncological parameters in an orthotopic Panc02 mouse model of pancreatic ductal adenocarcinoma (PDAC). The results showed that SkQ1 treatment led to increased levels of pro-angiogenic factors in the model and primarily constructed an anti-inflammatory cytokine microenvironment. At the cellular level, we found an increase in the proportion of memory T cells and a decrease in the frequency of natural killer T (NKT) cells. However, SkQ1 did not improve oncological parameters in tumor-bearing mice. New studies are needed to elucidate the reasons for the lack of therapeutic and/or preventive effects of this antioxidant. [1]

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Background: Chronic pancreatitis is one of the major risk factors for pancreatic cancer. Oxidative stress is considered to play a key role in both acute and chronic pancreatitis. In this regard, the recently reported mitochondrial-targeting antioxidant SkQ1 has been able to effectively scavenge reactive oxygen species at nanomolar concentrations. Therefore, we aimed to investigate the effects of SkQ1 on tissue damage and pain in acute and chronic pancreatitis. Methods: Acute and chronic pancreatitis were induced in C57BL/6 mice by intraperitoneal injection of secretin and treated with oral SkQ1. Hyperalgesia was assessed by behavioral observation and abdominal mechanosensitivity measurement. Serum and pancreatic tissue were collected for lipase analysis and histological examination. Results: SkQ1 had no effect on pain, serological or histological parameters of tissue damage in acute pancreatitis. In chronic pancreatitis, pain-related behaviors were significantly reduced (p < 0.0001), but histological grading showed that tissue damage was aggravated in the SkQ1-treated group (p = 0.03). Conclusion: SkQ1 treatment did not alleviate tissue damage in acute pancreatitis, but aggravated tissue damage in chronic pancreatitis. However, we found that it has an analgesic effect on chronic pancreatitis. Further research is needed to elucidate the risks and benefits of mitochondrial-targeting antioxidants as analgesics. [2]
Visomitin is a mitochondria-targeted antioxidant being developed for the treatment of various diseases involving oxidative stress, including eye disorders and neurodegenerative diseases. It is a valuable tool for studying the role of mitochondrial oxidative stress in disease and for developing new therapeutic strategies.

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

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

Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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)

Solubility in Formulation 1: ≥ 2.5 mg/mL (4.05 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 2: 2.5 mg/mL (4.05 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 2.5 mg/mL (4.05 mM) (saturation unknown) in 10% EtOH + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one),clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

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Solubility in Formulation 4: ≥ 2.5 mg/mL (4.05 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one),clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix well.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 5: ≥ 2.5 mg/mL (4.05 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one),clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix evenly.

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 (Please use freshly prepared in vivo formulations for optimal results.)