BAM15

Verified against PubChem PUG REST, CID 565708 — returned formula C16H10F2N6O, MW 340.29, IUPAC name 5-N,6-N-bis(2-fluorophenyl)-[1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-diamine, InChIKey OEGJBRZAJRPPHL-UHFFFAOYSA-N, CAS 210302-17-3; cross-referenced to CHEMBL3627755 and CHEBI:233585. Fields marked “not verified” are ones we could not confirm against a primary chemical database — we leave them blank rather than guess.

Identity, and a persistent misclassification

BAM15 is verified in PubChem as CID 565708: molecular formula C16H10F2N6O, molecular weight 340.29 g/mol, CAS 210302-17-3, InChIKey OEGJBRZAJRPPHL-UHFFFAOYSA-N, cross-referenced to CHEMBL3627755. Structurally it is an oxadiazolopyrazine core carrying two 2-fluorophenylamino groups — a fully synthetic heterocycle with no amino acids in it.

It is worth stating plainly because a substantial number of catalogues list BAM15 under peptides, and at least one lists it as 'BAM15 peptide'. It is not a peptide, has no sequence, and peptide-specific purity conventions, reconstitution assumptions and storage expectations do not transfer to it. A reader encountering purity claims framed in peptide terms for this compound is reading something written by someone who did not check the structure.

One further identifier caveat surfaced during verification. Some synonym lists attach the number 998-894-9 to BAM15 alongside the CAS number. That is a European Community (EC) inventory number, not a second CAS registry number, and it should not be reproduced as one. No UNII was confirmed for BAM15; some database dumps place the InChIKey in the UNII field, which is a data error rather than an identifier.

What uncoupling means, and what selectivity means here

Mitochondria generate ATP by using the electrochemical proton gradient across the inner membrane to drive ATP synthase. A protonophore carries protons across that membrane by an independent route, so the gradient dissipates and electron transport continues while producing proportionally less ATP. Substrate oxidation rises, oxygen consumption rises, and energy that would have been captured as ATP is released as heat. This is the same principle that made 2,4-dinitrophenol a weight-loss drug in the 1930s and the same principle that made it lethal.

The distinguishing property reported by Kenwood and colleagues in the original 2014 characterisation is that BAM15 depolarized the mitochondrial membrane without depolarizing the plasma membrane (PMID 24634817). Classical uncouplers including FCCP and DNP act at other membranes too, which produces effects unrelated to mitochondrial bioenergetics and confounds the measurement of mitochondrial function.

The comparison the original paper actually makes is with FCCP, at equal uncoupling potency. Against that benchmark, BAM15 stimulated a higher maximum rate of mitochondrial respiration in cultured cells and was less cytotoxic. The paper does not establish a numerical potency ratio against DNP, a point that matters given what circulates.

The rodent metabolic record

The most substantial animal work is Alexopoulos and colleagues in 2020, in male C57BL/6J mice fed a Western diet (PMID 32409697). Delivered as a 0.1% w/w diet admixture, the treated animals lost fat mass and increased nutrient oxidation without changes in food intake, lean body mass or body temperature, and without shifts in the biochemical and haematological markers of toxicity that were measured. The absence of a body-temperature change is a meaningful observation given that fatal hyperthermia is the mechanism by which DNP kills.

Hyperinsulinemic-euglycemic clamp studies in the same paper, with 9 chow, 7 Western-diet and 8 treated animals, reported improved insulin action across multiple tissue types. Hepatic fat and inflammatory lipids were reduced.

Chen and colleagues later ran a head-to-head comparison in female db/db mice against calorie restriction, semaglutide, rosiglitazone and niclosamide ethanolamine (PMID 37793464). BAM15 and calorie restriction improved body weight and liver steatosis more than the other three, while BAM15, semaglutide and rosiglitazone improved glucose tolerance more than calorie restriction did. Zhou and colleagues subsequently reported that combining BAM15 with the approved THR-beta agonist resmetirom outperformed either alone on energy expenditure, liver fat and glucose control in a mouse MASH model — while noting that no treatment altered liver fibrosis (PMID 39152636).

Where the direction of effect reverses

The literature outside metabolism is not uniform, and the inconsistency is instructive rather than embarrassing. In several models, uncoupling was reported to reduce mitochondrial reactive oxygen species, on the reasoning that lowering the proton-motive force shortens electron dwell time in the transport chain. Tsuji and colleagues, working in a cecal ligation and puncture mouse sepsis model, reported reduced mortality, reduced kidney tubule damage and reduced circulating and urinary mitochondrial DNA, with benefit still present when treatment began 12 hours after induction (PMID 36757801). Kenwood's original paper reported dose-dependent protection against acute renal ischemia-reperfusion injury in mice.

In cancer models the reported direction inverts. Gao and colleagues screened BAM15 against acute myeloid leukaemia cells and reported that it inhibited proliferation and promoted apoptosis, attributing the mechanism to disturbance of the reactive oxygen species balance, with efficacy in vivo and prolonged survival in treated mice (PMID 35192847).

Both cannot be a general property of the compound. The plain reading is that the direction depends on exposure, duration and cell type — sustained depolarization behaving differently from transient — and that any summary describing BAM15 as simply antioxidant or simply pro-oxidant is discarding half the record.

Separately, Cho and colleagues reported that 50 µM BAM15 reduced age-related mechanosensory neuron defects and extended mean lifespan in Caenorhabditis elegans (PMID 36422268).

The pharmacokinetics that were actually measured

One concrete pharmacokinetic dataset exists in the retrieved literature, and it is worth separating from the many figures quoted without one. In the Alexopoulos work, oral delivery in male C57BL/6J mice produced an average maximum plasma concentration of 8.2 µM with a half-life of 1.7 hours (PMID 32409697). Those are mouse numbers, by that route, in that strain.

A 1.7-hour half-life is short. It is short enough that it constrains what the compound can do on any infrequent administration schedule, and short enough to explain why medicinal chemistry effort has gone into derivatives. The compound is also reported as highly lipophilic with low aqueous solubility, which is why in vitro work generally dissolves it in DMSO and why the mouse studies used diet admixture rather than a simple aqueous vehicle.

Those two liabilities — short exposure and poor water solubility — are the explicit motivation for analog programmes that have generated hydroxylamine and hydrazine derivatives on the BAM15 scaffold. Reviewers of this literature have identified the delivery problem, rather than the mechanism, as the principal obstacle (PMID 37900126). No human pharmacokinetic data was located.

The human gap, and the literature about the claims

No human trial of BAM15 was found. A ClinicalTrials.gov search by intervention returned no BAM15 study; the only record surfacing was an unrelated monoclonal antibody trial matched on name similarity. No published human pharmacokinetic, safety or efficacy dataset was located in PubMed. There is no human dataset from which any statement about human effect, human exposure or human margin of safety could be derived.

This gap is not merely academic, and there is now peer-reviewed literature documenting what fills it. Turnock and Piatkowski published a study in Performance Enhancement & Health analysing discussion of BAM15 across two large bodybuilding forums and a YouTube instructional video and its comments. They report that the compound is framed within those communities as a low-risk alternative to DNP — the paper's title quotes a user calling it 'the new DNP' — and that a publicly accessible step-by-step synthesis guide contributed to normalising risk-taking, with commenters expressing intent to self-experiment despite the limited evidence.

That paper is cited here as evidence about how the claims circulate, not as evidence about the compound's effects. It is, at present, the only peer-reviewed source describing human use of BAM15 at all, and what it documents is unsupervised self-experimentation, not a trial.

What is not known

There is no human evidence of any kind for BAM15. No trial is registered on ClinicalTrials.gov, and no human pharmacokinetic, safety, dose-ranging or efficacy study was located in PubMed. Nothing is known about human absorption, exposure, clearance, interactions, or the margin between an effective and a harmful exposure, and the mouse pharmacokinetics — a 1.7-hour half-life after oral gavage in one strain — cannot be scaled into human predictions. The compound's low aqueous solubility and high lipophilicity are recognised in the literature as unsolved delivery obstacles, which is why analog programmes exist. The direction of effect on reactive oxygen species is not settled: cytoprotective in sepsis and kidney models, pro-oxidant and pro-apoptotic in cancer models, with the determining variables not established. No study has tested prolonged administration in any species for the effects that would matter most in sustained use, and no reproductive, developmental or carcinogenicity toxicology was found. The fatal history of 2,4-dinitrophenol is a reason for caution about this class generally rather than a comparison that resolves in BAM15's favour, because the comparison has never been made in humans for BAM15 at all.

Questions