People talk about BAM15 and SLU-PP-332 in metabolic research like they’re cousins. Fair enough, on the surface. Feed mice a fatty diet, add either one, and the mice end up leaner. Look closer and they have almost nothing in common. BAM15 leaks protons across the inner mitochondrial membrane, so fuel gets burned with no ATP to show for it. SLU-PP-332? It’s a small molecule that switches on the estrogen-related receptors (ERRs), and those turn on genes you’d normally see after a run. Below we walk through what the primary papers actually reported, and where the older internet copy on these two got it wrong.
Key findings
- Kenwood 2014: BAM15 came out of a library screen. Unlike FCCP it left the plasma membrane polarized, and cells tolerated it better.
- Alexopoulos 2020: obese mice lost fat mass on oral BAM15. Food intake? Same. Lean mass and body temperature? Also the same.
- Axelrod 2020: mice on BAM15 didn’t put on weight like controls, and their glucose handling looked better. In cells, AMPK stayed switched on.
- SLU-PP-332 is a pan-ERR agonist (ERRα, β and γ) with its highest potency at ERRα. It is not a peptide.
- Mice given SLU-PP-332 had more type IIa oxidative muscle fibers and ran longer, and the endurance effect depended on ERRα (Billon 2023).
- In obese and ob/ob mice, SLU-PP-332 raised energy expenditure and fatty acid oxidation and reduced fat mass gain (Billon 2024).
Two different levers on the same problem
Think of a cell’s energy budget like a hydroelectric dam. Pumps (the electron transport chain) push protons up behind the wall, and the turbine (ATP synthase) lets them fall back through to make ATP. Now drill a leak in the wall. Water still flows, the pumps work harder, but less of that work turns into ATP. The extra fuel just gets burned off.
That’s BAM15.
SLU-PP-332 doesn’t touch the dam at all. It sits upstream, at the level of transcription. ERRs are orphan nuclear receptors that, according to genetic studies, matter a lot for skeletal muscle exercise capacity [4]. Turn them on and the cell builds more mitochondrial machinery and leans harder on oxidative metabolism. So one compound wastes energy on purpose and the other builds more capacity to burn it. You can see why people keep putting them in the same sentence, and also why they aren’t interchangeable.
BAM15: the uncoupler that behaved itself
Chemical uncouplers aren’t new. 2,4-dinitrophenol and FCCP have been around for decades, and both have the same problem. They also mess with other membranes, including the plasma membrane, which leads to depolarization, mitochondrial inhibition and cell death at concentrations not far from the useful ones.
Kenwood and colleagues at the University of Virginia went looking for something cleaner. Out of a small library screen popped a fluorinated oxadiazolopyrazine with a mouthful of a chemical name. They called it BAM15 [1]. Matched to FCCP at equal potency, cells on BAM15 hit a higher top respiration rate and more of them survived. The plasma membrane stayed polarized. Oh, and it worked in live mice too: animals given it before a renal ischemia-reperfusion insult came through with less kidney damage.
Honestly, the first pitch for BAM15 was as a cleaner lab tool. If you want to measure maximal mitochondrial respiration without confounding off-target effects, that’s still a perfectly good reason to reach for it.
What the BAM15 obesity papers measured
Two groups published mouse obesity work in 2020, and they line up fairly well.
Alexopoulos and colleagues reported that BAM15 was orally bioavailable, increased nutrient oxidation and lowered body fat mass in diet-induced obese mice [2]. Here’s what we find more telling. The mice ate the same amount. Their lean mass didn’t budge, body temperature didn’t either, and blood toxicity panels looked normal. Liver fat dropped. So did inflammatory lipids. When the team ran clamp studies, insulin sensitivity was up in more than one tissue.
The Pennington Biomedical group (Axelrod and colleagues) put C57BL/6J mice on a high-fat diet with BAM15, and those mice just didn’t gain like the controls did [3]. In a dish, respiration sped up and cells pulled in more nutrients, with AMPK stuck in the on position. Weirdly, body composition and blood sugar control got better independent of the weight change. Their explanation: the drug piles up in lipid-rich tissue.
One correction worth making. Older copy online (including the previous version of this page) claimed BAM15 shifts body temperature. The Alexopoulos data say the opposite, at least in that model. We’d also flag that several authors on both papers disclosed financial ties to a company developing uncouplers, which is normal in this field but good to know when you read the results.
SLU-PP-332: an exercise mimetic, not a peptide
Let’s clear up the biggest error first. You’ll see SLU-PP-332 described around the web as a “modified peptide.” It isn’t. It’s a small synthetic molecule. That matters for how you handle it, how you analyze it and how you read the literature.
Billon, Burris and colleagues reported it in 2023 as an ERR pan agonist that hits all three subtypes, with the highest potency at ERRα [4]. ERRα agonists had been hard to make, so this was a real gap being filled. In a skeletal muscle cell line it increased mitochondrial function and cellular respiration. Mice given the compound had more type IIa oxidative fibers and better endurance. And the endurance effect needed ERRα specifically.
The follow-up came in 2024. In diet-induced obese and ob/ob mice, SLU-PP-332 raised energy expenditure and fatty acid oxidation, lowered fat mass accumulation and improved insulin sensitivity [5].
The old page quoted an ERRα EC50 of 98 nM. We couldn’t confirm that figure from an abstract we could check, so it’s gone. If you need potency numbers for your assay, go to the full 2023 paper and pull them yourself.
There’s also a regulatory footnote. A 2026 paper from the UCLA Olympic Analytical Laboratory mapped 22 in vitro metabolites of SLU-PP-332 using human liver S9 fractions, specifically for doping-control testing, and notes that WADA prohibits exercise mimetics and metabolic modulators in sport [6]. The anti-doping labs are clearly paying attention to this one. For more on the compound alone, see our SLU-PP-332 compound page.
Side by side
| BAM15 | SLU-PP-332 | |
|---|---|---|
| Compound type | Small-molecule protonophore | Small-molecule ERR agonist |
| Primary target | Inner mitochondrial membrane (proton leak) | ERRα, β, γ (most potent at ERRα) |
| Main readouts in mice | Lower fat mass, better insulin sensitivity, less liver fat | More oxidative fibers, longer running, higher energy expenditure |
| Food intake (reported) | Unchanged (Alexopoulos 2020) | Not addressed in the abstracts we read |
| Key papers | Kenwood 2014; Alexopoulos 2020; Axelrod 2020 | Billon 2023; Billon 2024 |
What’s still missing
Nearly everything here is mouse and cell work. There are no published human trials for either compound that we could find. Long-term toxicology is thin. And we haven’t seen a single paper that puts BAM15 and SLU-PP-332 in the same experiment, which is a shame, because a head-to-head comparison of an uncoupler and an ERR agonist on the same diet model would answer a lot of questions people currently guess at.
If you’re comparing exercise mimetics more broadly, our piece on SLU-PP-332 vs 5-Amino-1MQ covers another pairing, and the BAM15 compound page has the basic chemistry.
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 to 123. PMID 24634817
- 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. PMID 32409697
- Axelrod CL, King WT, Davuluri G, et al. BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control. EMBO Mol Med. 2020;12(7):e12088. PMID 32519812
- Billon C, Sitaula S, Banerjee S, et al. Synthetic ERRα/β/γ agonist induces an ERRα-dependent acute aerobic exercise response and enhances exercise capacity. ACS Chem Biol. 2023;18(4):756 to 771. PMID 36988910
- Billon C, Schoepke E, Avdagic A, et al. A synthetic ERR agonist alleviates metabolic syndrome. J Pharmacol Exp Ther. 2024;388(2):232 to 240. PMID 37739806
- Avliyakulov NK, Sobolevsky T, Ahrens E. Analysis and identification of in vitro metabolites of exercise mimetic SLU-PP-332 ERRα/β/γ agonist for doping-control purposes. Drug Test Anal. 2026;18(3):439 to 450. PMID 41688415
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