BAM15
Research Guide

Research Overview

BAM15 is a small-molecule mitochondrial protonophore, commonly described in the literature as a selective mitochondrial uncoupler. It is worth flagging at the outset that BAM15 is not a peptide, although some vendor catalogs mislabel it as one. Structurally it is a fluorophenyl-substituted oxadiazolopyrazine, and its identity is well characterized in public chemistry databases (PubChem CID 565708, CAS 210302-17-3).

The compound was first reported by Kenwood and colleagues in 2014 as a mitochondrial uncoupler that increases the proton permeability of the inner mitochondrial membrane without depolarizing the plasma membrane. That plasma-membrane selectivity is the feature most often cited to distinguish BAM15 from classical uncouplers such as FCCP and 2,4-dinitrophenol (DNP), and it is associated in the source literature with lower reported in-vitro cytotoxicity at comparable uncoupling potency to FCCP.

This page summarizes the reported identity, mechanism, and preclinical research applications of BAM15 for laboratory reference. Every value below traces to a cited source retrieved for this dossier. All framing is in-vitro or animal-model and reported. No human efficacy has been established, and no human clinical trials for BAM15 the mitochondrial uncoupler were found.

Mechanism Summary

Mechanisms reported in the in-vitro and preclinical research literature include:

• BAM15 is reported to act as a protonophore at the inner mitochondrial membrane. By increasing proton permeability, it dissipates the proton-motive force (the electrochemical gradient across the membrane), so that electron transport runs uncoupled from ATP synthase. In the source models this is reported to raise mitochondrial respiration and oxygen consumption and to increase cellular energy expenditure, while lowering the ATP yield per unit of substrate oxidized.
• The defining characteristic in the original characterization (Kenwood et al. 2014) is that BAM15 depolarizes the mitochondrial membrane without depolarizing the plasma membrane. This selectivity is what separates it from FCCP and DNP in the literature and is linked to its lower reported in-vitro cytotoxicity at uncoupling potency comparable to FCCP.
• Downstream signaling reported in preclinical and cell models includes activation of AMPK and PGC-1alpha, which are linked to mitochondrial biogenesis and oxidative metabolism, and engagement of mitochondrial quality-control pathways including PINK1 and LC3-II associated mitophagy. Uncoupling has been reported to lower mitochondrial reactive oxygen species (mtROS) in some models by reducing electron dwell time in the transport chain, for example in sepsis and kidney work. Other models report pro-oxidant or pro-apoptotic effects at higher exposures, for example in cancer cell studies. All of this is reported in-vitro or preclinical context; no human effect is implied.

Reference Data

Identity values are compiled from public chemistry databases and vendor documentation. Confirm the exact salt form, molecular weight, and purity for a given batch against its Certificate of Analysis (COA).

Research Applications

In laboratory research, BAM15 is studied in contexts such as:

• Diet-induced obesity and body-fat models: studied in diet-induced obese mice, where oral BAM15 was reported to reduce fat mass and increase nutrient oxidation without changing food intake, lean mass, or body temperature (Alexopoulos et al. 2020, PMID 32409697).
• Insulin sensitivity and glycemic control: investigated in mouse models (db/db and diet-induced obesity) and in hyperinsulinemic-euglycemic clamp studies, reported to improve insulin action across tissues and reduce gluconeogenic enzyme expression (Alexopoulos et al. 2020; review PMC10600450).
• Fatty-liver models (NAFLD/NASH/MASH): studied in mouse models and isolated liver mitochondria, with reported reductions in hepatic fat, triglycerides, and oxidative stress; also investigated in combination with the THR-beta agonist resmetirom (MGL-3196) in a fatty-liver mouse model (Zhou et al. 2024, Acta Physiologica).
• Sepsis and sepsis-associated acute kidney injury: studied in a cecal ligation and puncture mouse sepsis model, with reported reductions in mortality, kidney tubule damage, and circulating or urinary mitochondrial DNA and mtROS (JCI 2023, PMC10065071).
• Renal ischemia-reperfusion and cold-storage tubule injury: investigated for reported protective effects against acute renal ischemic-reperfusion injury in mouse kidney models.
• Cancer cell biology: studied in vitro and in xenograft models (breast cancer, acute myeloid leukemia, melanoma), where sustained mitochondrial depolarization was reported to raise superoxide and activate caspase-3/7 apoptotic signaling (review PMC10600450; AML study S0006295222000429).
• Aging and neurodegeneration models: studied in Caenorhabditis elegans, where BAM15 was reported to relieve age-related neurodegeneration and extend lifespan (Cho et al. 2022, PMC9698188).
• Inflammation and innate immunity: reported in macrophage and LPS-injected mouse models to inhibit NLRP3 inflammasome activation and shift macrophage polarization (review PMC10600450).
• Skeletal muscle mitochondrial quality control: investigated in vivo for reported effects on mitophagy and mitochondrial biogenesis in muscle.
• Cardiometabolic and atherosclerosis models: explored via RNA-seq, molecular docking, and experimental verification as a candidate mechanism in atherosclerosis models (Sci Rep 2025, s41598-025-98209-3).
• Medicinal-chemistry and analog development: BAM15 serves as a scaffold for improved-pharmacokinetics uncouplers, with hydroxylamine and hydrazine derivatives synthesized to address its short reported half-life and low water solubility (Quinlan et al. 2024; ScienceDirect S0968089624004590).

Storage Information

• Physical form, exact color, and lot-specific HPLC purity are not fixed across sources and should be read from the batch COA supplied with the material rather than assumed.
• BAM15 is reported in the literature to have low water solubility and high lipophilicity and is commonly dissolved in DMSO for in-vitro work. Recommended reconstitution solvent, working stock concentration, and solubility limits for the actual product should come from the COA and product documentation.
• For general handling of lyophilized and solid research materials, see the Lyophilized Storage Guide. For preparing working stocks from a solid, see the Reconstitution Calculator. Storage temperature and long-term stability for the specific product should be confirmed against the COA and product documentation.