5HT1F receptor ligands that induce mitochondrial biogenesis


Technology: MUSC investigators have used manual curation and traditional medicinal chemistry techniques to synthesize 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.  Several of these compounds were tested and found to induce MB in naïve mice as well. These molecules are proposed to be useful for the treatment of diseases, pathologies, or syndromes in which mitochondria are impaired or in which increasing mitochondrial capacity would be beneficial. For example, these compounds could be useful for the treatment of acute kidney injury (AKI), which currently has no treatment.


Overview: Mitochondrial damage is implicated in many pathologies, such as neurodegeneration, heart disease, heart attack, stroke, renal dysfunction, liver dysfunction, type 2 diabetes and central numerous system disorders. In addition, genetic mitochondrial diseases include Leber's hereditary optic neuropathy, diabetes mellitus, mental disorders/diseases, Leigh's disease, mitochondrial encephalomyopathy, 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

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. "5-HT1F receptor regulates mitochondrial homeostasis and its loss potentiates." American Journal of Physiology-Renal Physiology, 2018 doi: 10.1152/ajprenal.00077.2018.



Inventors: Christopher Lindsey, Craig Beeson, Rick Schnellman

Patent Status: PCT/US17/59651

MUSC-FRD Technology ID: P16103


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