Peptigrade

Metabolic & Weight

BAM15

N5,N6-bis(2-fluorophenyl)[1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-diamine·Also known as: BAM-15, furazano[3,4-b]pyrazine mitochondrial uncoupler, CAS 210302-17-3, PubChem CID 565708

FDARegulatory status

Not approved for human use. Investigational small molecule in preclinical / early clinical development; no NDA, no FDA-recognized indication, and no public evidence of an open IND for BAM15 in the United States as of April 2026.

WADARegulatory status

Not individually named on the 2026 WADA Prohibited List. Classification would most plausibly fall under S0 (non-approved substances) for any athlete given that BAM15 has no marketing authorization in any jurisdiction; a specific athlete wishing to use BAM15 should assume it is unavailable under sport rules.

Regulatory note ·BAM15 is sold legally in the United States only as a research chemical for in-vitro and animal studies. Continuum Biosciences (co-founded by Webster Santos and Kyle Hoehn, 2017) licensed Virginia Tech patents covering BAM15 and adjacent furazano[3,4-b]pyrazine uncouplers and has publicly described an obesity / NAFLD development program. No BAM15 Phase 1, Phase 2, or Phase 3 trial is currently listed on ClinicalTrials.gov as of April 2026; no peer-reviewed human PK, safety, or efficacy data has been published. Medicinal-chemistry work to improve solubility and half-life (BAM15's short ~1.7 h t½ and high lipophilicity are known formulation liabilities) continues — Gruber 2024 published unsymmetric hydroxylamine and hydrazine derivatives benchmarked against BAM15 (IC₅₀ 0.27 μM).

§ The quick take

TL;DR · Editor’s summary

BAM15 is an investigational small-molecule mitochondrial protonophore — not a peptide — that has the cleanest preclinical obesity-reversal dataset of any uncoupler since 2,4-DNP was pulled from the market in 1938. The important distinction from DNP is that BAM15 depolarizes the mitochondrial inner membrane without depolarizing the plasma membrane (Kenwood 2014, Tomar 2021 via dipole-potential dependence), and across mouse studies it does not raise body temperature, does not suppress food intake, and preserves lean mass while reducing fat mass (Alexopoulos 2020, Nat Commun; Kirkland 2020, EMBO Mol Med). Ma 2024 ran a head-to-head in female db/db mice against semaglutide, rosiglitazone, NEN, and calorie restriction — BAM15 matched or exceeded the incretin on glucose tolerance, beat both on weight normalization, and retained the most lean mass of any weight-reducing arm. That is a striking preclinical package.

The honest gap: there is no human evidence. No BAM15 Phase 1, Phase 2, or Phase 3 trial is listed on ClinicalTrials.gov as of April 2026, no human PK has been published, and no safety database beyond rodents and C. elegans exists in the peer-reviewed literature. Continuum Biosciences licensed the Virginia Tech patents and has described an obesity / NAFLD development program, but a published Phase 1 read-out is not available. Known formulation liabilities — short half-life (~1.7 h), high lipophilicity, limited aqueous solubility — are the reason medicinal chemistry programs (Gruber 2024) continue to iterate on the scaffold.

Under the Peptigrade rubric, a strong, replicated rodent dataset with zero human data earns a D, not a C; a successful Phase 1 human read-out would be the trigger for reassessment upward. The compound should not be conflated with 2,4-DNP, but it also should not yet be used in humans outside a registered trial.

§ Grade matrix

The grade
per outcome.

One peptide can earn very different grades for different uses. Here is every outcome we’ve graded for BAM15, sorted by strength of evidence.

D

Diet-induced obesity / weight loss

Weak

Strong and independently replicated rodent evidence: Alexopoulos 2020 (Nat Commun) in HFD-fed C57BL/6J mice and Kirkland 2020 (EMBO Mol Med) showed reversal of diet-induced obesity with preserved lean mass, no hyperthermia, and intact food intake. No human efficacy trial has been published. Grade does not clear C without any human data.

6 studiesUpdated 2026-04-21
D

Insulin resistance & glycemic control

Weak

Alexopoulos 2020 normalized fasting glucose and glucose tolerance in HFD mice; Ma 2024 head-to-head in female db/db mice matched semaglutide and rosiglitazone on glucose tolerance and outperformed them on weight normalization. AMPK-mediated glucose uptake characterized mechanistically. No human T2D trial.

4 studiesUpdated 2026-04-21
D

NAFLD / hepatic steatosis

Weak

Reduced hepatic triglyceride content in HFD-mice (Alexopoulos 2020) and decreased liver fat in db/db mice more effectively than semaglutide or rosiglitazone (Ma 2024). Mechanistically coherent via increased hepatic β-oxidation. No NASH biopsy endpoint data in humans.

4 studiesUpdated 2026-04-21
Pend.

Acute systemic inflammation (sepsis / LPS models)

Pending · Below evidence threshold

Cheng 2021 showed pretreatment reduced IL-6, TNF-α, and hepatic inflammation in the LPS mouse model via AMPK-linked macrophage reprogramming. Single-lab signal, pretreatment-dependent. No human inflammation data.

2 studiesUpdated 2026-04-21
Ins.

Cancer cell proliferation (breast)

Insufficient

Childress 2021 (Cancer & Metabolism) reported suppression of breast cancer proliferation in vitro through ATP depletion in high-glycolysis lines. In-vitro only; no in-vivo tumor-growth model for BAM15 has been published, and cancer is not the primary clinical target.

1 studiesUpdated 2026-04-21
Ins.

Healthspan / lifespan extension

Insufficient

Liu 2022 extended lifespan and reduced neurodegeneration in aged C. elegans. Invertebrate model with no mammalian replication for the longevity endpoint; does not support any human claim.

1 studiesUpdated 2026-04-21

§ Why this grade

Sub-scores for this outcome.

Diet-induced obesity / weight loss

Every grade rolls up six weighted sub-scores, each rated 1 to 5 with a written justification. Here is how the top-outcome grade was constructed.

Mechanism understood

4 / 5

Protonophore cycle characterized in planar bilayers (Tomar 2021), mitochondrial selectivity mapped to membrane dipole potential, downstream AMPK signaling and substrate-oxidation shift documented in rodent tissues (Kirkland 2020, Alexopoulos 2020). Not all mechanistic claims validated in humans.

Human studies (count + quality)

1 / 5

No human trial published, no human trial registered on ClinicalTrials.gov. Zero patients treated with BAM15 in the peer-reviewed literature as of April 2026.

Effect vs placebo

1 / 5

No placebo-controlled human trial has been run. Animal vs vehicle effect is large and replicated across labs, but animal-vs-vehicle is not the same as human-vs-placebo under this rubric.

Long-term safety data

1 / 5

Longest published exposure is rodent (weeks). No human safety data. Historical class precedent (2,4-DNP) means the absence of a human safety record is weighted heavily.

Side effect profile

3 / 5

Mouse data shows no hyperthermia, no food-intake suppression, no detectable tissue toxicity, and normal hematology/chemistry at 10–50 mg/kg PO. Absence of a human adverse-event database caps this score at 3 regardless of how clean the preclinical record is.

Regulatory status

1 / 5

Not FDA-approved; no public evidence of an open IND for BAM15 as of April 2026; no marketing authorization in any jurisdiction; not individually named by WADA but plausibly S0-classed for any competing athlete. Sold only as a research chemical for laboratory use.

§ What the science says

How BAM15
works.

Plain-English explanation of the molecule and its proposed mechanism, written at an 8th-grade reading level so anyone can engage with it. Every claim is linked to a primary source below.

What it is

BAM15 is a small-molecule mitochondrial protonophore uncoupler (C₁₆H₁₀F₂N₆O, MW 340.29 g/mol, CAS 210302-17-3, PubChem CID 565708) built around a fused [1,2,5]oxadiazolo[3,4-b]pyrazine heterocycle with two 2-fluorophenyl anilines at the N5 and N6 positions. Unlike peptide entries in this database, BAM15 is a synthetic small molecule, not a protein or peptide. It was first described by Kenwood and Hoehn in Molecular Metabolism (2014) in the Santos lab at Virginia Tech. The aniline N-H is the ionizable group responsible for protonophoric activity; the extended π-system delocalizes the anion after deprotonation and allows the molecule to shuttle protons across the inner mitochondrial membrane in both protonated and deprotonated forms. Selectivity for mitochondrial inner membrane over plasma membrane is driven by the difference in membrane dipole potential between the two membranes (Tomar 2021). The compound is a solid off-white to pale-yellow powder handled from DMSO stock for in-vitro work and dosed orally (10–50 mg/kg in mice) in preclinical in-vivo studies. It is not a peptide, not a metabolite, and not a natural product.

How it works

  1. 01

    Mitochondrial protonophore (inner-membrane selective)

    BAM15 acts as a classical weak-acid protonophore: it picks up a proton in the acidic intermembrane space, diffuses across the inner mitochondrial membrane as the neutral species, releases the proton in the alkaline matrix, and returns as the membrane-permeable anion — short-circuiting the proton-motive force without engaging ATP synthase (Kenwood 2014, Mol Metab; Tomar 2021, BBA Biomembranes). The distinguishing feature versus FCCP is that BAM15's protonophoric activity is strongly modulated by membrane dipole potential, which is high in the mitochondrial inner membrane and lower in the plasma membrane. Phloretin (a dipole-potential reducer) suppresses BAM15's activity on planar bilayers, confirming the dipole-dependent mechanism. At 270 nM EC₅₀ for uncoupling in L6 myoblast mitochondria, BAM15 does not depolarize the plasma membrane — the safety property that separates it from both FCCP and 2,4-DNP.

  2. 02

    Increased substrate oxidation and energy expenditure

    By dissipating the proton gradient, BAM15 drives electron-transport-chain turnover to maintain proton pumping, raising oxygen consumption without proportional ATP synthesis. In HFD-fed C57BL/6J mice at 10–50 mg/kg PO daily (Alexopoulos 2020, Nat Commun), this produced normalization of body weight without a change in food intake and without a change in body temperature. Substrate utilization shifted toward increased β-oxidation and glucose oxidation, and hepatic triglyceride content dropped. Kirkland 2020 (EMBO Mol Med) independently reproduced the effect in both prevention and treatment paradigms without tachyphylaxis over multi-week dosing.

  3. 03

    AMPK activation and metabolic reprogramming

    Lowered cellular ATP/AMP ratio activates AMP-activated protein kinase. Kirkland 2020 showed AMPK-dependent enhancement of skeletal-muscle glucose uptake, ACC phosphorylation (suppressing lipogenesis), and activation of fatty-acid oxidation. Chronic AMPK signaling is the proposed route for PGC-1α upregulation and mitochondrial biogenesis reported in follow-on work. This mechanism overlaps with metformin's downstream signature but is driven by a fundamentally different proximal trigger (membrane-potential dissipation vs Complex I partial inhibition).

  4. 04

    Preserved lean mass — the feature that distinguishes BAM15 from calorie restriction

    In the Ma 2024 head-to-head in female db/db mice (Mol Metab), BAM15 retained the largest percentage of lean mass among all weight-reducing arms, including semaglutide, rosiglitazone, and calorie restriction. The mechanistic reading is that increased mitochondrial turnover of fatty acids and glucose does not trigger the muscle-catabolic adaptive response that restricted intake or GLP-1-mediated anorexia produce. This is the reason BAM15 is interesting at all in a market where GLP-1 agonists already deliver large weight-loss effects.

  5. 05

    Anti-inflammatory signal via immunometabolic reprogramming

    Cheng 2021 (Int J Mol Sci) showed that BAM15 pretreatment reduced IL-6, TNF-α, and IL-10 in LPS-challenged mice and downregulated M1-macrophage polarization genes. Interpretation: reduced cellular ATP availability limits the energy-intensive M1 inflammatory program, mimicking the anti-inflammatory effect of caloric restriction without actual food restriction. This is a single-lab signal in an acute model; chronic inflammatory-disease models for BAM15 have not been published.

  6. 06

    What is NOT known about the mechanism in humans

    Every mechanistic statement above comes from rodent, cell-culture, or planar-bilayer work. No human PK has been published. The reported ~1.7 h half-life and high lipophilicity are rodent / in-silico values — they have not been validated in human subjects. The concentration range that uncouples mouse mitochondria in vivo has not been mapped to a human plasma exposure. Whether BAM15 produces the same lean-mass-preserving, temperature-neutral profile in humans at therapeutically uncoupling exposures is the central open question, and it is exactly what a well-designed Phase 1 MAD would answer.

§ Investigated uses

What it’s
been studied for.

Investigated does not mean proven. This list shows every use that appears in the published literature, regardless of evidence strength. See the grade matrix above for which ones have actually held up.

  • Diet-induced obesity (HFD mouse models)

    Alexopoulos 2020 (Nat Commun), Kirkland 2020 (EMBO Mol Med) — independent labs, consistent effect

  • Type 2 diabetes / glycemic control

    Ma 2024 head-to-head in db/db mice vs semaglutide, rosiglitazone, NEN, calorie restriction

  • NAFLD / hepatic steatosis

    Reduction in liver triglyceride content in multiple HFD and db/db preclinical studies

  • Sepsis / acute inflammation

    Cheng 2021 LPS mouse model — single-lab pretreatment signal

  • Breast cancer cell proliferation

    Childress 2021 — in-vitro only

  • Aging / neurodegeneration

    Liu 2022 in C. elegans — invertebrate lifespan + neuroprotection

  • Cardiac and ischemia-reperfusion

    Exploratory animal / cell work; no pivotal dataset

  • Mechanistic research tool (Seahorse XF, isolated mitochondria)

    Standard laboratory use at 100 nM – 1 μM

§ The honest gaps

What we don’t
know yet.

Every peptide page on this site is required to include this section. Absence of evidence is information. If we don’t flag the gaps, we’re lying by omission.

  • !

    No human trial of BAM15 has been registered on ClinicalTrials.gov or published in the peer-reviewed literature as of April 2026. No human PK, no human safety database, no dose-response, no food-effect data.

  • !

    Whether the lean-mass-preserving, temperature-neutral profile seen in mice at 10–50 mg/kg PO will hold in humans at therapeutically uncoupling plasma exposures is the key unanswered question. Narrow therapeutic window is the historical failure mode of this drug class (2,4-DNP).

  • !

    The human pharmacokinetic profile is unknown. The reported ~1.7 h half-life is preclinical; human t½, bioavailability, and food effects have not been published. Formulation for consistent human exposure remains an open engineering problem.

  • !

    Long-term cardiac safety at sustained uncoupling exposure has not been characterized in any mammal at human-relevant durations. Tachycardia, cardiac remodeling, and arrhythmogenic potential are historical red flags for mitochondrial uncouplers.

  • !

    Off-target uncoupling in tissues where high ATP demand is critical (myocardium, retina, cochlea, CNS) has not been directly tested at chronic-exposure concentrations. The membrane-dipole selectivity argument is a tissue-membrane argument, not a tissue-ATP-demand argument.

  • !

    Drug–drug interactions are unstudied. The AMPK-activating effect raises specific questions about combination use with metformin, GLP-1 agonists, and SGLT2 inhibitors — the drugs BAM15 would most plausibly be used alongside.

  • !

    Whether the Continuum Biosciences / Virginia Tech clinical candidate will be BAM15 itself or one of the Gruber 2024-class derivatives with improved solubility and half-life is not clear from the public record. Derivatives may have a different safety and PK profile than the parent.

  • !

    No reproductive, developmental, or long-term carcinogenicity data has been published.

§ On YouTube

What experts and
influencers say.

We index YouTube content discussing BAM15and tag every speaker by credential and trust level. The goal is not to summarize the internet — it’s to tell you which voices to weight.

  • BAM15 and the New Generation of Mitochondrial Uncouplers

    Peter Attia MD·MD, longevity medicine

    Walks through the Kenwood / Alexopoulos / Kirkland preclinical story and is explicit that BAM15 has no human trial and should not be confused with 2,4-DNP despite the shared mechanism class.

    Verified credentials

  • Mitochondrial Uncoupling for Obesity — What the Science Actually Shows

    Rhonda Patrick — FoundMyFitness·PhD, biomedical science

    Frames BAM15 as a research tool with a striking preclinical signal and explicitly warns against self-experimentation given the absence of human PK, the narrow-therapeutic-window history of the class, and the lack of formulation.

    Verified credentials

  • BAM-15 Fat Loss Experiment — My 30 Day Results

    Anonymous biohacker·Unverified

    Self-dosing anecdote from a research-chemical supplier. No assay of purity, no plasma concentration, no safety monitoring beyond bodyweight. Do not weight against the preclinical literature and do not interpret as human evidence.

    Caution — anecdotal

§ Citations

Every claim,
linked to source.

All 12 sources informing this page, with DOI or PubMed identifiers. Click through to the primary literature.

  1. [01]

    Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane

    Kenwood BM, Weaver JL, Bajwa A, et al. · Mol Metab · 2014

    In vitroPMID 24392247
  2. [02]

    Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice

    Alexopoulos SJ, Chen SY, Brandon AE, et al. · Nat Commun · 2020

    AnimalPMID 32409697
  3. [03]

    BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control

    Kirkland RA, Arrieta J, Finck BN, et al. · EMBO Mol Med · 2020

    AnimalPMID 32519812
  4. [04]

    Protonophoric action of BAM15 on planar bilayers, liposomes, mitochondria, bacteria and neurons

    Firsov AM, Khailova LS, Knorre DA, et al. · BBA Biomembranes · 2021

    In vitroPMID 32971482
  5. [05]

    Head-to-head comparison of BAM15, semaglutide, rosiglitazone, NEN, and calorie restriction on metabolic physiology in female db/db mice

    Ma H, Alexopoulos SJ, Turner N, et al. · Mol Metab · 2024

    AnimalPMID 37793464
  6. [06]

    BAM15, a mitochondrial uncoupling agent, attenuates inflammation in the LPS injection mouse model

    Cheng CW, Kuo CY, Fan CC, et al. · Int J Mol Sci · 2021

    AnimalDOI
  7. [07]

    Breast cancer growth and proliferation is suppressed by the mitochondrial-targeted furazano[3,4-b]pyrazine BAM15

    Childress ES, Alexopoulos SJ, Hoehn KL, Santos WL · Cancer Metab · 2021

    In vitroDOI
  8. [08]

    BAM15 relieves neurodegeneration in aged Caenorhabditis elegans and extends lifespan

    Liu L, Liu C, Fang Z, et al. · Front Aging Neurosci · 2022

    AnimalPMID 36422268
  9. [09]

    BAM15 as a mitochondrial uncoupler: a promising therapeutic agent for diverse diseases

    Zhao Y, Wang J, Liu H, et al. · J Transl Med · 2023

    Systematic reviewPMID 37900126
  10. [10]

    Unsymmetric hydroxylamine and hydrazine BAM15 derivatives as potent mitochondrial uncouplers

    Gruber T, Schillinger C, Reischl M, et al. · Eur J Med Chem · 2024

    In vitroPMID 39740573
  11. [11]

    BAM15 — Compound summary (CID 565708)

    National Center for Biotechnology Information · PubChem · 2026

    RegulatoryLink
  12. [12]

    WADA 2026 Prohibited List (in force January 1, 2026) — Section S0 Non-Approved Substances

    World Anti-Doping Agency · WADA · 2026

    RegulatoryLink

§ Adjacent peptides

Worth reading
alongside this.

Compare

Semaglutide

FDA-approved incretin-class standard of care for obesity (~15% weight loss in STEP-1). BAM15 matched or exceeded semaglutide on glucose tolerance and weight normalization in the Ma 2024 db/db head-to-head — but in mice, without any human data.

Read its grades

Compare

Tesofensine

Another non-incretin obesity mechanism (monoamine reuptake inhibition) at the Phase 2b stage. Useful comparator for how Peptigrade grades a compound with a strong efficacy signal but incomplete pivotal infrastructure — tesofensine at least has human data; BAM15 does not yet.

Read its grades

Compare

AOD-9604

A cautionary comparator: 'fat-loss molecule' with preclinical signal that did not replicate in adequately powered humans. Tests the rule that mouse obesity reversal is not a clinical finding.

Read its grades

Compare

SLU-PP-332 (pipeline)

ERR agonist being developed for similar 'exercise-mimetic / metabolic' indications. Grouped with BAM15 as mechanistically novel, preclinically striking, human-evidence-free compounds the functional-medicine market is already discussing.

Read its grades

Compare

5-Amino-1MQ (pipeline)

NNMT inhibitor targeting adipose NAD/SAM metabolism — another mitochondrial / metabolic-rewiring small molecule with rodent-only efficacy data. Shares BAM15's 'interesting preclinical, no human trial' profile.

Read its grades

Where to research further

Looking for BAM15
for laboratory research?

Peptigrade does not sell peptides. RiboCore is one supplier we track that publishes batch-level certificates of analysis (mass spec, HPLC purity) for research-grade material. We have no commercial relationship with them — listing here is editorial.

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