Mitochondrial diseases exhibit clinical heterogeneity and can manifest at any age. The treatment of mitochondrial disorders has posed significant challenges due to the multi-organ involvement observed in various mitochondrial diseases. Small molecules play a pivotal role in facilitating drug development, and Protheragen offers a comprehensive small molecule drug discovery platform to expedite the research process for clients targeting mitochondrial diseases.
Small Molecule Drugs for Mitochondrial Diseases
The treatment of mitochondrial diseases involves the utilization of a variety of small molecule drugs that target distinct aspects of mitochondrial function and cellular metabolism.
- Molecules Bypassing Mitochondrial Complex I Deficiency
Idebenone, acting as an electron carrier and antioxidant, has been evaluated in mitochondrial and neurodegenerative diseases with potential benefits.
- Agents Enhancing Electron Transfer Chain Function
Coenzyme Q10 (CoQ10) and riboflavin exhibit antioxidant properties and have shown efficacy in certain mitochondrial diseases. Dichloroacetate (DCA) and thiamine enhance pyruvate dehydrogenase activity, promoting flux into the citric acid cycle. Sonlicromanol, lipoic acid, and glutathione enhance antioxidant defenses and mitochondrial function.
- Agents Regulating NADH/NAD+ Rati
Compounds such as pyruvate, AICAR, nicotinamide riboside, and acipimox aim to restore the NADH/NAD+ balance, potentially improving glycolysis and mitochondrial function.
Fig.1 NAD+-Mediated Rescue of Mitochondrial Function. (Russell, O. M., et al., 2020)
- Agents Restoring Nitric Oxide Production
Arginine and citrulline act as NO precursors, potentially benefiting conditions like stroke-like episodes in MELAS syndrome.
- Agents Regulating Autophagy
Rapamycin and urolithin A stimulate mitophagy, offering potential therapeutic benefits in mitochondrial disorders.
- Agents as Cardiolipin Protectors
Elamipretide binds to cardiolipin, preserving its function and improving cardiac mitochondrial function.
- Agents as Energy Buffer
Creatine and taurine stabilize cellular bioenergetics and show neuroprotective effects in various conditions.
Fig.2 Small molecules for mitochondrial disorders. (Meng, L., et al., 2023)
Our Services
The development of small molecule drugs is a highly technology-intensive and intricate process, encompassing knowledge from diverse disciplines such as chemistry, biology, and pharmacology, among others. Protheragen offers an experienced team and essential resources to generate authentic and reliable experimental results in support of the development of small molecule drugs for mitochondrial diseases.
Discovery and Screening
- Identify potential small molecule compounds through various methods such as virtual screening, high-throughput screening, or rational drug design.
- Conduct initial screening assays to evaluate the compounds' efficacy, selectivity, and safety profiles.
- Prioritize lead compounds based on their activity against specific molecular targets or pathways relevant to mitochondrial diseases.
Lead Optimization
- Conduct medicinal chemistry studies to optimize the chemical structure of lead compounds for improved potency, selectivity, and pharmacokinetic properties.
- Evaluate the lead compounds in vitro and in vivo to assess their efficacy, toxicity, and metabolic stability.
- Iteratively refine the chemical structure through structure-activity relationship (SAR) studies to enhance drug-like properties and minimize adverse effects.
Our Advantages
Whether you require assistance in the field of small molecule drug development or any other aspect of mitochondrial disease research, our team is committed to providing tailored solutions to effectively address your challenges. If you are interested in availing our services, please feel free to contact us.
References
- Russell, O. M.; et al. (2020). Mitochondrial Diseases: Hope for the Future. Cell, 181(1), 168–188.
- Meng, L., & Wu, G. (2023). Recent advances in small molecules for improving mitochondrial disorders. RSC advances, 13(30), 20476–20485.
