Energy balance
The mitochondrial uncoupler SHO1122147, administered at 200 mg/kg/day, significantly reduces body weight and liver triglycerides in a mouse model of MASH without causing hyperthermia or altering food intake.
This research identifies a specific compound (SHO1122147) that acts as a mitochondrial uncoupler to burn energy directly, leading to significant fat loss and improved liver health in a mouse model of fatty liver disease. Crucially, it achieved this without causing dangerous overheating or reducing the amount of food eaten. While not yet available for humans, it represents a potential future therapeutic class that targets energy expenditure rather than appetite, potentially avoiding the muscle loss and gastrointestinal side effects seen in current popular weight loss drugs.
In a Gubra-Amylin (GAN) mouse model of MASH, SHO1122147 was efficacious in decreasing body weight and liver triglyceride levels at 200 mg kg−1 day−1 without changes in body temperature.
Why this rating
High-quality preclinical data (in vivo efficacy, PK, safety) but lacks human clinical trials.
Source
Design, Synthesis, and Biological Evaluation of [1,2,5]Oxadiazolo[3,4-<i>b</i>]pyridin-7-ol as Mitochondrial Uncouplers for the Treatment of Obesity and Metabolic Dysfunction-Associated Steatohepatitis
Mary A. Foutz et al. · Journal of Medicinal Chemistry · 2024
DOI 10.1021/acs.jmedchem.4c02366
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