5HT1F receptor ligands that induce mitochondrial biogenesis


Technology: MUSC investigators have synthesized new chemical entity analogues for 5HT1F receptors. These structurally unique novel chemical entities act as agonists to the serotonin class-1F (5HT1F) receptors and were found to be potent inducers of mitochondrial biogenesis (MB) in vitro.  Also, several of the compounds were tested and found to induce MB in naïve mice. These molecules are proposed to be useful for the treatment of diseases or pathologies, in which mitochondria are impaired or in which increasing mitochondrial capacity would be beneficial. For example, these investigators have demonstrated in a nephrotoxic serum (NTS) model of glomerular disease that a novel 5HT1F receptor ligand attenuates albuminuria in mice treated with drug compared to control (figure 1).

Overview: Mitochondrial damage is implicated in many pathologies, including central nervous system disorders, heart disease, heart attack, stroke, renal dysfunction, liver dysfunction, and diabetes. In addition, genetic mitochondrial diseases include Leber's hereditary optic neuropathy, diabetes mitochondrial encephalomyopathy, Leigh's disease, lactic acidosis, and stroke-like episodes (MELAS), etc. Therefore, agents that interact with the 5-HT1F receptor to improve or repair mitochondrial function, or increase mitochondrial capacity would be useful for treatment of these conditions.


Applications: Treatment of mitochondrial dysfunctions and diseases, including renal dysfunction, stroke, heart attack, diabetes and nervous system disorders

Advantages:  Structurally unique from other 5HT1F receptor-specific ligands and induce mitochondrial biogenesis

Key Words: Mitochondrial biogenesis, 5-HT1F, Serotonin, cheminformatics, pharmacophore, drug discovery, drug development


Publications:  Gibbs et al. (2018) "5-HT1F receptor regulates mitochondrial homeostasis and its loss potentiates acute kidney injury and impairs renal recovery." Am J Physiol Renal Physio, doi: 10.1152/ajprenal.00077.2018.


Scholpa et al. (2018) “5-HT(1F) receptor-mediated mitochondrial biogenesis for the treatment of Parkinson's disease.” Br J Pharmacology, doi: 10.1111/bph.14076.


Gibbs et al. (2018) “Identification of dual mechanisms mediating 5-hydroxytryptamine receptor 1F-induced mitochondrial biogenesis” Am J Physiol Renal Physiol, doi:10.1152/ajprenal.00324.2017.


Scholpa et al. (2017). Mitochondrial-Based Therapeutics for the Treatment of Spinal Cord Injury: Mitochondrial Biogenesis as a Potential Pharmacological Target. J Pharmacol Exp Ther, doi: 10.1124/jpet.117.244806.


Inventors: Christopher Lindsey, Craig Beeson, Rick Schnellman, Yuri Peterson

Patent Status: PCT/US17/59651; US16/347,163

MUSC-FRD Technology ID: P16103


Patent Information:
For Information, Contact:
Scott Davis
Associate Director, Licensing
MUSC Foundation for Research Development
Christopher Lindsey
Craig Beeson
Rick Schnellmann
Yuri Peterson
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