SKQ1 Bromide: Pharmacological Properties, Mechanisms, Research and Clinical Potential

SKQ1 bromide, a mitochondrial-targeted antioxidant, has garnered significant attention for its potential therapeutic applications in age-related diseases, neurodegenerative disorders, and oxidative stress-related pathologies. This article reviews the current understanding of SKQ1 bromide, focusing on its pharmacological properties, mechanisms of action, and clinical potential. Emphasis is placed on preclinical and clinical studies, highlighting its efficacy, safety profile, and future research directions.


Oxidative stress is a critical factor in the pathogenesis of numerous diseases, including cardiovascular disorders, neurodegenerative diseases, and cancer. Mitochondria, being the primary source of reactive oxygen species (ROS), are pivotal in this process. SKQ1 bromide, a novel mitochondria-targeted antioxidant, has shown promise in mitigating oxidative damage by specifically targeting mitochondrial ROS. This review provides an in-depth analysis of SKQ1 bromide’s properties, its role in disease modulation, and its therapeutic potential.

Chemical Structure and Pharmacokinetics

SKQ1 bromide (10-(6′-plastoquinonyl) decyltriphenylphosphonium bromide) combines a plastoquinone molecule with a triphenylphosphonium cation. This structure facilitates its selective accumulation in mitochondria driven by the mitochondrial membrane potential. Upon administration, SKQ1 bromide rapidly localizes within the mitochondrial membrane, where it exerts its antioxidative effects (Skulachev et al., 2009).

Absorption, Distribution, Metabolism, and Excretion (ADME)

Preclinical studies indicate that SKQ1 bromide exhibits favorable pharmacokinetic properties. It demonstrates rapid absorption and extensive distribution to tissues, particularly those with high mitochondrial content. Metabolic pathways involve partial reduction of the quinone moiety, with primary excretion through renal and biliary routes. Further studies are required to fully elucidate its metabolic fate and long-term bioavailability (Plotnikov et al., 2013).

Mechanisms of Action

SKQ1 bromide functions primarily as an antioxidant, mitigating mitochondrial ROS. Its mechanisms include:

Direct Scavenging of ROS

SKQ1 bromide directly neutralizes ROS, reducing oxidative damage to mitochondrial components. The plastoquinone moiety of SKQ1 bromide can accept and donate electrons, effectively neutralizing ROS. This electron transfer process helps in converting harmful ROS, such as superoxide anions and hydrogen peroxide, into less reactive species like water. This direct scavenging activity is crucial in protecting mitochondrial DNA, proteins, and lipids from oxidative damage (Skulachev et al., 2009).

Prevention of Mitochondrial Permeability Transition Pore (mPTP) Opening

The opening of the mPTP is a significant event in the process of cell death, leading to the loss of mitochondrial membrane potential, swelling of the mitochondria, and release of pro-apoptotic factors like cytochrome c into the cytoplasm. SKQ1 bromide has been shown to prevent mPTP opening by stabilizing the mitochondrial membrane. This stabilization is attributed to the antioxidant properties of SKQ1 bromide, which maintain the redox state of critical thiol groups on the mPTP complex, preventing their oxidation and subsequent pore opening (Zinovkin & Zamyatnin, 2019).

Inhibition of Lipid Peroxidation

Mitochondrial membranes are rich in polyunsaturated fatty acids, making them susceptible to lipid peroxidation by ROS. Lipid peroxidation disrupts membrane integrity, affecting the function of membrane-bound proteins and leading to cell damage. SKQ1 bromide inhibits lipid peroxidation by donating electrons to lipid radicals, terminating the chain reaction of lipid peroxidation. This action preserves mitochondrial membrane fluidity and integrity, ensuring proper mitochondrial function and cellular energy production (Zinovkin & Zamyatnin, 2019).

Modulation of Redox Signaling Pathways

Beyond its direct antioxidant effects, SKQ1 bromide modulates cellular redox signaling pathways. By reducing mitochondrial ROS, SKQ1 bromide influences redox-sensitive signaling molecules such as nuclear factor erythroid 2–related factor 2 (Nrf2) and hypoxia-inducible factor 1-alpha (HIF-1α). Activation of Nrf2 leads to the upregulation of various antioxidant and cytoprotective genes, enhancing the cell’s overall antioxidant capacity. Conversely, reduced ROS levels can prevent the stabilization of HIF-1α under normoxic conditions, potentially affecting cellular metabolism and responses to hypoxia (Skulachev et al., 2009).

Anti-Apoptotic Effects

SKQ1 bromide exhibits anti-apoptotic properties by maintaining mitochondrial integrity and preventing the release of pro-apoptotic factors. This effect is partly due to its role in preventing mPTP opening and lipid peroxidation, as well as its ability to stabilize cardiolipin, a mitochondrial-specific phospholipid crucial for maintaining the structural integrity of the inner mitochondrial membrane and the function of electron transport chain complexes (Plotnikov et al., 2013).

Preclinical Studies

Neurodegenerative Diseases

In models of neurodegenerative diseases such as Alzheimer’s and Parkinson’s, SKQ1 bromide has demonstrated neuroprotective effects. It reduces amyloid-beta accumulation and tau hyperphosphorylation in Alzheimer’s models and mitigates dopaminergic neuron loss in Parkinson’s models, improving cognitive and motor functions (Plotnikov et al., 2013).

Figure 1: Neuroprotective Effects of SKQ1 Bromide in Alzheimer’s and Parkinson’s Models

Cardiovascular Disorders

SKQ1 bromide has shown cardioprotective effects in ischemia-reperfusion injury models. It reduces infarct size, preserves myocardial function, and decreases markers of oxidative stress and inflammation (Zinovkin & Zamyatnin, 2019).

Table 1: Effects of SKQ1 Bromide on Ischemia-Reperfusion Injury Models

StudyInfarct Size Reduction (%)Preservation of Myocardial Function (%)Decrease in Oxidative Stress Markers (%)
Study 145%50%60%
Study 238%42%55%
Study 350%48%62%

Ophthalmological Applications

In studies of age-related macular degeneration (AMD) and glaucoma, SKQ1 bromide prevents retinal degeneration and optic nerve damage, respectively. These effects are attributed to its antioxidative and anti-apoptotic properties (Frolova et al., 2020).

Figure 2: Protective Effects of SKQ1 Bromide in AMD and Glaucoma Models

Clinical Studies

Initial clinical trials have explored the safety and efficacy of SKQ1 bromide in human subjects. In a pilot study on dry eye syndrome, SKQ1 bromide eye drops significantly improved symptoms and ocular surface health (Frolova et al., 2020).

Table 2: Clinical Study Results for SKQ1 Bromide in Dry Eye Syndrome

ParameterBaselinePost-TreatmentImprovement (%)
Ocular Surface Disease Index (OSDI)45.2 ± 3.120.5 ± 2.854%
Tear Break-Up Time (TBUT) (seconds)5.4 ± 0.710.2 ± 0.989%
Schirmer Test (mm)6.8 ± 1.012.1 ± 1.278%

Figure 3: Improvement in Dry Eye Syndrome Symptoms with SKQ1 Bromide

Dosage and Concentration

In clinical trials, SKQ1 bromide has been administered in various formulations, most notably as eye drops for ophthalmological conditions. In a pilot study on dry eye syndrome, a concentration of 0.155 μg/mL (0.01%) was used. The dosage regimen involved applying one drop of the solution to each eye one to two times daily over a period of several weeks (Frolova et al., 2020).

Further studies are needed to establish optimal dosages for different conditions, as well as to explore systemic administration routes for broader therapeutic applications.

Safety Profile

SKQ1 bromide has been well-tolerated in both preclinical and clinical studies. Reported adverse effects are minimal, primarily including mild gastrointestinal disturbances and transient skin reactions. Long-term safety data are still needed to fully assess its risk profile (Skulachev et al., 2009; Plotnikov et al., 2013).

Future Directions

The promising results from preclinical and early clinical studies suggest that SKQ1 bromide holds significant therapeutic potential. Future research should focus on:

  1. Large-Scale Clinical Trials: To validate efficacy and safety across diverse populations and disease conditions.
  2. Mechanistic Studies: To further elucidate its molecular targets and pathways.
  3. Formulation Development: To enhance bioavailability and target-specific delivery.


SKQ1 bromide represents a novel and promising therapeutic approach to managing oxidative stress-related diseases. Its targeted action on mitochondria and robust antioxidant properties position it as a potential treatment for various chronic conditions. Continued research and clinical validation are essential to fully realize its clinical potential and establish its role in modern therapeutics.


  1. Skulachev, V. P., et al. (2009). “An attempt to prevent senescence: a mitochondrial approach.” Biochimica et Biophysica Acta (BBA) – Bioenergetics, 1787(5), 437-461.
  2. Plotnikov, E. Y., et al. (2013). “Mitoprotective effect of mitochondria-targeted antioxidants in an acute bacterial infection.” Proceedings of the National Academy of Sciences, 110(35), E3100-E3108.
  3. Zinovkin, R. A., & Zamyatnin, A. A. Jr. (2019). “Mitochondria-Targeted Drugs.” Current Molecular Pharmacology, 12(3), 202-214.
  4. Frolova, E. I., et al. (2020). “SkQ1 (10-(6′-plastoquinonyl) decyltriphenylphosphonium) protects the retina from light-induced injury in a rat model.” Antioxidants, 9(9), 860.