BAM15 (CAS 210302-17-3; chemical name (2-fluorophenyl){6-[(2-fluorophenyl)amino](1,2,5-oxadiazolo[3,4-e]pyrazin-5-yl)}amine) is a small-molecule mitochondrial protonophore uncoupler — it is not a peptide. It was identified in 2014 by Kenwood and colleagues in the Hoehn laboratory (University of Virginia / University of New South Wales) during a screen for mitochondrial uncouplers that lack the off-target plasma-membrane depolarization activity of older protonophores such as FCCP and 2,4-dinitrophenol (DNP) [1]. The compound transports protons across the inner mitochondrial membrane, uncoupling nutrient oxidation from ATP synthesis and increasing the rate of mitochondrial respiration. In rodent diet-induced obesity (DIO) models, oral BAM15 has been reported to decrease body fat mass, improve insulin sensitivity, and reduce hepatic steatosis without altering food intake or lean body mass [3].
BAM15 has not been investigated in human clinical trials. The published research base is entirely preclinical — mouse DIO models, in vitro mitochondrial respiration assays, and mechanistic structure–activity work. BAM15 is not approved by the FDA, EMA, or any other regulatory authority for any indication, and is not in active regulatory development as a drug candidate. The compound belongs to the mitochondrial protonophore uncoupler class, which historically includes 2,4-dinitrophenol — a compound with documented acute mammalian lethality at supratherapeutic amounts that resulted in its removal from human therapeutic use in the late 1930s and that continues to cause deaths in unsupervised weight-loss use. BAM15 is structurally distinct from DNP and has been characterized as having a wider in vitro therapeutic window in cell systems, but the protonophore mechanism class as a whole carries acute mammalian toxicity risk that has not been resolved in any human-clinical-development program for any protonophore to date.
Researchers should interpret BAM15 as a preclinical research-tool compound for mitochondrial-function and metabolic-research applications, not as an obesity therapeutic candidate with established human-equivalent amount protocols. The compound is supplied here in capsule format for laboratory research; the constituents of any human-equivalent amount translation are not available in the peer-reviewed literature.
Important Note on the Evidence Base
Important note on the evidence base and the protonophore mechanism class: BAM15 belongs to the mitochondrial protonophore uncoupler chemical class, which includes 2,4-dinitrophenol (DNP). DNP was marketed as a weight-loss drug in the 1930s and was withdrawn from human therapeutic use after cases of hyperthermia, cataracts, and acute death at supratherapeutic amounts. DNP continues to be associated with mortality in unsupervised weight-loss contexts, with case reports and toxicology literature consistently identifying it as one of the more lethal weight-loss substances when used outside of controlled research settings. BAM15 is structurally distinct from DNP and has been described in the foundational Kenwood 2014 work as not depolarizing the plasma membrane — the off-target activity that contributes to DNP’s narrow therapeutic index [1]. BAM15 has been reported in cell and rodent systems to maximally stimulate mitochondrial respiration over a broad amount-range without causing respiratory collapse. However, no protonophore uncoupler has been successfully advanced through human clinical development for any indication, and the protonophore mechanism class as a whole carries acute mammalian toxicity risk that has not been resolved in any human program. Published BAM15 research is preclinical only (rodent DIO models, in vitro mitochondrial respiration, structure–activity characterization). Researchers should consult the primary literature for rodent protocol detail rather than extrapolating to human-equivalent amounts, and should be specifically aware of the class-level toxicity profile when evaluating the compound for any research context.
Mechanism of Action
BAM15 is a lipophilic weak-acid mitochondrial protonophore. It carries protons across the inner mitochondrial membrane independently of ATP synthase, dissipating the electrochemical proton gradient that normally drives oxidative phosphorylation. The net effect is that nutrient oxidation (electron transport chain activity) becomes uncoupled from ATP production, with the energy released as heat rather than captured as ATP. Cells respond by increasing oxygen consumption and substrate oxidation to maintain ATP demand.
Distinction from older protonophores. The 2014 Kenwood paper that first characterized BAM15 framed the compound’s defining feature as a lack of plasma-membrane depolarizing activity. Older protonophore uncouplers including FCCP and DNP have well-documented off-target activity at the plasma membrane, where their protonophoric behavior depolarizes the cell and produces cytotoxic effects unrelated to mitochondrial uncoupling proper. This off-target activity contributes substantially to the narrow therapeutic index that has prevented protonophore uncouplers from advancing through human clinical development. BAM15 was identified specifically in a screen designed to find mitochondrial uncouplers that retained the on-target activity while losing the plasma-membrane off-target activity [1].
Structure-activity characterization. Follow-up work by Kenwood and colleagues in 2015 characterized the furazano[3,4-b]pyrazine scaffold underlying BAM15, identifying the structural features required for selective mitochondrial protonophore activity without plasma-membrane depolarization [2]. The compound has an in vitro EC50 of approximately 270 nM in L6 myoblast mitochondria. Compared to FCCP at equivalent uncoupling potency, BAM15 stimulates a higher maximum rate of mitochondrial respiration in cell systems.
Rodent DIO model effects. The Alexopoulos 2020 study in Nature Communications reported that oral BAM15 administered to mice on a western-diet obesigenic protocol decreased body fat mass without altering food intake, lean body mass, body temperature, or measured biochemical and hematological markers in the rodent system [3]. The study also reported decreased hepatic fat, decreased inflammatory lipid species, and improved insulin sensitivity in hyperinsulinemic-euglycemic clamp studies. These findings have been the most widely cited preclinical-efficacy results for BAM15 in the metabolic-research literature. The rodent findings have not been reproduced in any peer-reviewed human clinical trial.
Available Forms
Omnix Peptides supplies BAM15 in a single research format. Each lot is independently characterized by HPLC and LC–MS, with a batch-specific Certificate of Analysis available on the product page.
- BAM15 Capsules 50 mg, 60-count — oral capsule format. The capsule format supports in vitro and ex vivo research workflows; the published rodent literature has used oral administration (chow-supplementation and gavage) in the DIO obesity model and intraperitoneal injection in acute mechanism studies.
BAM15 is classified under the Metabolic & Weight Research research category. For research framed around non-uncoupler mitochondrial mechanism classes in the metabolic neighborhood, see the MOTS-c hub (a 16-amino-acid mitochondrial-derived peptide with proposed AMPK-mediated effects, mechanistically distinct from protonophore uncoupling) and the 5-Amino-1MQ hub (a small-molecule NNMT inhibitor with proposed NAD+-axis effects, also mechanistically distinct).
Note on Administration
No established human administration exists for BAM15. The published research is preclinical only, consisting of rodent diet-induced obesity studies and in vitro mitochondrial respiration assays. The protonophore uncoupler mechanism class — which includes 2,4-dinitrophenol — carries acute mammalian toxicity risk at supratherapeutic amounts that has not been resolved for any compound in the class in any human-clinical-development program. Researchers should consult the primary literature cited in the References section directly for rodent protocol detail (administration route, vehicle composition, treatment duration), and should not extrapolate to human-equivalent amounts. Body-surface-area allometric scaling and other standard interspecies amount-translation approaches are not appropriate for compounds in this mechanism class without dedicated human pharmacokinetic and safety data, which have not been published for BAM15.
Frequently Asked Questions
Is BAM15 FDA-approved?
No. BAM15 is not approved by the FDA, EMA, or any other regulatory authority for any indication, and is not in active regulatory development as a drug candidate. The published research base is entirely preclinical — rodent diet-induced obesity studies, in vitro mitochondrial respiration assays, and structure-activity characterization. BAM15 has not been investigated in human clinical trials.
Is BAM15 the same as DNP (2,4-dinitrophenol)?
No. BAM15 and 2,4-dinitrophenol (DNP) are structurally distinct molecules. They are both members of the mitochondrial protonophore uncoupler chemical class, meaning they both shuttle protons across the inner mitochondrial membrane and uncouple nutrient oxidation from ATP synthesis. BAM15 was identified specifically in a screen designed to find mitochondrial uncouplers that retain the on-target uncoupling activity while losing the plasma-membrane depolarization off-target activity that contributes to DNP’s narrow therapeutic index. However, the protonophore mechanism class as a whole carries acute mammalian toxicity risk at supratherapeutic amounts that has not been resolved in any human-clinical-development program for any protonophore to date. DNP has been associated with hyperthermia, cataracts, and acute death in unsupervised weight-loss use, and is a well-documented cause of death in the toxicology literature.
What is the mitochondrial protonophore mechanism class?
Protonophores are lipophilic weak-acid molecules that transport protons across biological membranes. In mitochondria, they shuttle protons across the inner mitochondrial membrane independently of ATP synthase, dissipating the electrochemical proton gradient that normally drives oxidative phosphorylation. The cellular consequence is that nutrient oxidation (electron transport chain activity) becomes uncoupled from ATP production, with the energy released as heat rather than captured as ATP. The class includes 2,4-dinitrophenol, FCCP, CCCP, and BAM15 among others. Compounds in this class are widely used as research tools in mitochondrial biology, but have not been successfully advanced through human clinical development for any indication.
What rodent models has BAM15 been studied in?
The most widely cited rodent BAM15 work is the Alexopoulos 2020 Nature Communications study in mice on a western-diet obesigenic protocol (diet-induced obesity, DIO). In that study, oral BAM15 administration was reported to decrease body fat mass, decrease hepatic fat, decrease inflammatory lipids, and improve insulin sensitivity by hyperinsulinemic-euglycemic clamp, without altering food intake or lean body mass in the rodent system. BAM15 has also been investigated in rodent models of acute kidney injury (ischemia-reperfusion), sepsis, and other inflammation-associated conditions in the broader preclinical literature, though the metabolic-research applications have received the most attention.
Why does BAM15 not have a published amount protocol in this hub?
No established human administration exists for BAM15. The published research is preclinical only, and the protonophore mechanism class carries acute mammalian toxicity risk at supratherapeutic amounts that has not been resolved for any compound in the class in any human-clinical-development program. Surfacing rodent amount protocols in a structured amount section creates an implicit human-equivalent translation that is not defensible for this compound class. Researchers should consult the primary preclinical literature directly for rodent protocol detail and should not extrapolate to human-equivalent amounts.
How does BAM15 differ from MOTS-c or 5-Amino-1MQ?
All three compounds appear in the metabolic-research neighborhood but operate through different molecular mechanism classes. BAM15 is a mitochondrial protonophore uncoupler that acts directly on the inner mitochondrial membrane, dissipating the proton gradient. MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded in the mitochondrial 12S rRNA gene, with proposed effects mediated through AMPK signaling and metabolic adaptation pathways. 5-Amino-1MQ is a small-molecule inhibitor of nicotinamide N-methyltransferase (NNMT) with proposed effects on NAD+ availability and methylation balance. The three mechanism classes are non-overlapping; the literatures are entirely separate.
References
- Kenwood BM, Weaver JL, Bajwa A, et al. Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane. Mol Metab. 2014;3(2):114-123. doi:10.1016/j.molmet.2013.11.005 · PubMed: 24634817
- Kenwood BM, Calderone JA, Taddeo EP, Hoehn KL, Santos WL. Structure-activity relationships of furazano[3,4-b]pyrazines as mitochondrial uncouplers. Bioorg Med Chem Lett. 2015;25(21):4858-4861. doi:10.1016/j.bmcl.2015.06.040 · PubMed: 26119501
- Alexopoulos SJ, Chen SY, Brandon AE, et al. Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice. Nat Commun. 2020;11(1):2397. doi:10.1038/s41467-020-16298-2 · PubMed: 32409697
For Research Use Only. The products described on this page are sold strictly for in vitro laboratory research and are not intended for human or animal consumption, diagnostic use, or therapeutic use. The published research summarized above is provided as scientific reference material. Nothing on this page constitutes medical advice, a therapeutic claim, or a recommendation for any use outside of a properly resourced and ethically reviewed research setting.
