BAM15

Molecular identity

Sequence

Non-peptide small molecule — C16H10F2N6O, 340.29 g/mol (CAS 1830574-08-1); a lipophilic fluorinated heteroaromatic mitochondrial uncoupler, not an amino-acid sequence.

Formula

C16H10F2N6O

Molecular weight

340.29 g/mol

CAS

1830574-08-1

PubChem CID

565708

What it acts on

• Proton gradient across the inner mitochondrial membrane — described as a chemical uncoupler that dissipates the gradient, disrupting the coupling between electron transport and ATP synthesis and, in the review literature, raising mitochondrial respiration and energy expenditure.
• Mitochondrial ROS output — the sepsis paper specifies that the gradient is dissipated without generating mtROS, and reports that BAM15 prevented septic-serum-driven mtROS overproduction in kidney tubule cells in vitro; the atherosclerosis paper reports lower mtROS and less oxidised mitochondrial DNA.
• Release of mitochondrial DNA as a damage signal — in the cecal-ligation-and-puncture mouse model, plasma and urinary mtDNA rose after the insult and fell after treatment, while injected exogenous mtDNA reproduced the inflammation and kidney injury on its own.
• NLRP3/ASC/caspase-1 inflammasome and GSDMD-mediated pyroptosis — in ApoE-deficient mice and in ox-LDL-treated primary aortic endothelial cells, inflammasome activation and pyroptosis markers were reported as reduced, and the NLRP3 activator nigericin partially reversed that effect.
• Hepatic lipid handling alongside thyroid hormone receptor-β signalling — in a mouse steatohepatitis model, combining BAM15 with a THR-β agonist outperformed either agent alone on energy expenditure and liver fat, with the body-fat component attributed to BAM15.

What the studies report

Each item below summarises the paper it is numbered to, written from that paper's own abstract. The badge says how the evidence was produced.

1. 1.
   animal modelJ Clin Invest (2023)

   An in vivo mouse study of polymicrobial sepsis induced by cecal ligation and puncture, with fluids and antibiotics as background care and BAM15 introduced either at the time of the insult or later, once the animals were already ill. The paper reports reduced mortality — including in the late group — along with less kidney damage and less splenic apoptosis. Plasma and urinary mitochondrial DNA rose after the insult and fell after treatment, and cultured kidney tubule cells exposed to septic serum showed mtROS overproduction and mtDNA release that the compound prevented. The authors mark their own boundaries: the benefit depended on neutrophils, since neutrophil depletion counteracted it, and a large exogenous mitochondrial DNA load reversed the protection. They position the compound as a candidate in experimental sepsis, not as an established treatment.

2. 2.
   reviewFront Endocrinol (Lausanne) (2023)

   A narrative review rather than primary data. It sets out the mechanism — disrupting the coupling between electron transport and ATP synthesis, dissipating the proton gradient, increasing mitochondrial respiration and energy expenditure — and surveys the preclinical literature across obesity, diabetes, non-alcoholic fatty liver disease, sepsis and cardiovascular disease. The authors call the reported tolerability encouraging, but name the obstacles themselves: high lipophilicity, the need for alternative delivery methods, and the fact that further research is required before therapeutic potential in clinical settings can be judged.

3. 3.
   animal modelAtherosclerosis (2025)

   ApoE-deficient mice on a high-fat diet served as the atherosclerosis model, with mouse primary aortic endothelial cells exposed to oxidised LDL as the parallel in vitro system. The report describes smaller plaques, less lipid deposition and lower serum IL-1β and IL-18 in treated animals, alongside reduced mitochondrial ROS and less oxidised mitochondrial DNA. Western blotting showed lower GSDMD-NT, NLRP3, ASC and cleaved caspase-1. The authors' own control is informative about the limits of the claim: the NLRP3 activator nigericin only partially reversed the protection, which supports a central role for the inflammasome without establishing it as the sole route. The work is entirely mouse and cell culture.

4. 4.
   animal modelActa Physiol (Oxf) (2024)

   A treatment study in male C57BL/6J mice fed the GAN diet to model metabolic dysfunction-associated steatohepatitis, comparing the THR-β agonist MGL-3196, BAM15, the combination, and untreated control. Treatments were admixed in the diet and animals were pair-fed so that drug intake could be controlled for. The combination outperformed either single agent on energy expenditure, liver fat loss, glucose control and fatty liver disease activity score, and the paper separates the contributions: ALT, liver mass and plasma cholesterol tracked with the THR-β agonist, while change in body fat tracked with BAM15. The authors state explicitly that no treatment altered liver fibrosis, and present the result as warranting further investigation rather than as a conclusion.

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