SS-31 (elamipretide) is a small-molecule peptide comprising four amino acids; specifically targeting mitochondria.
Efficient penetration of cell membranes is one of its key features, with a precise target of the inner mitochondrial membrane.
Traditional antioxidants fail to adequately accumulate within the more confined mitochondrial matrix, scavenging excess reactive oxygen species (ROS) as a major constraint.
The unique design of SS-31 allows for both neutralization of free radicals, and various electrostatic interactions/hydrophobic interactions; specific anchoring to mitochondria itself being a direct result of this.
Mitochondrial medicine as a whole sees SS-31 as one of the more attainable near-future drugs.
Beyond the purely cytoprotective effects, potent reparative actions are also observed.
Breaking the previously intractable vicious cycle of oxidative stress is what sets SS-31 apart.
Improving myocardial energy metabolism, smaller infarct sizes, overall cardiac function, and to some extent, neurodegenerative function, are all within reach.
Exercise tolerance and muscle strength are additional, yet important, endpoints that SS-31 is capable of influencing.
Sequence
D-Arg-Dmt-Lys-Phe-NH2; Dmt=2',6'-dimethylTyr
CAS Number
736992-21-5
Molecular Formula
C32H49N9O5
Molecular Weight
639.8 g/mol
Research Of SS-31
1.Clinical Applications and Therapeutic Potential
Early clinical trials have demonstrated significant cytoprotective effects – primary mitochondrial myopathies, Barth syndrome, heart failure, acute kidney injury and dry eye syndrome all representing promising areas of therapeutic application.
2.Antioxidant Effects
Conventional antioxidants are widely distributed but as stated above lack the specific penetration.
SS-31’s physicochemical properties enable that all important selective accumulation.
The electron donor (dimethyltyrosine) directly interacts with and neutralizes the free radicals generated within the electron transport chain.
Source level interruption of oxidative stress is the fundamental goal; protection of mitochondrial DNA, constant (optimal) maintenance of the microenvironment, and essentially, lifelong energy production, is the end result of all of the above.
Slowing or halting aging processes and a wide range of previously untreatable diseases, are the end goals of this line of research.
3.Improving systemic energy status impaired by cancer and chemotherapy
In skeletal muscle of cancer patients, mitochondrial dysfunction is the primary cause of reduced ATP synthesis; irreversible muscle atrophy and subsequent deformation follow as a direct result.
SS-31 effectively suppresses cachexia, prevents a reduction in glycolytic muscle fiber area, blocks mitochondrial loss and various forms of abnormal autophagy/mitosis.
Analysis of skeletal muscle, liver, and plasma metabolites indicates significant alterations in both energy and protein metabolism within the tumor host.
4.Improving mitochondrial dysfunction and associated memory impairment
Endotoxin-treated mice exhibit all aspects of this mitochondrial dysfunction – oxidative stress, inflammatory responses, neuronal apoptosis, hippocampal dendritic spine loss – learning and simple memory capabilities as the outcome.
Experiments show SS-31’s protective effects against the earlier mentioned factors; modulation of Brain-derived neurotrophic factor, or abrineurin BDNF signaling as a key pathway.
Reversal of some synaptic signaling protein alterations and increased (physiological) structural complexity of synapses is observed.
Therapeutic potential for oxidative stress/neuroinflammation type damage is evident.
5.Inhibiting mitochondrial permeability transition pore (mPTP) opening to prevent apoptosis
SS-31 indirectly maintains inner mitochondrial membrane integrity, through both antioxidant and stable ATP synthesis effects.
Direct action on adenine nucleotide translocator (ANT) pushes up the threshold for mitochondrial permeability transition pore /mPTP opening.
Abnormal premature activation of this process is successfully inhibited; acute conditions (myocardial infarction, stroke as representative cases) can be at least partially treated by this line of inhibition.
6.Inhibition of an Inflammatory Response
All the above are interlinked.
Mitochondrial function is improved, damage is reduced, and all downstream effects of chronic or acute inflammation are at least partially mitigated.
SS-31’s full therapeutic value lies in these combined, yet fundamental, anti-inflammatory actions.
COA
HPLC
MS
