BAM15 — Mitochondrial Protonophore Uncoupler (Metabolic Tool Compound)

BAM15 is an orally bioavailable, mitochondria-targeted protonophore uncoupler that increases nutrient oxidation and energy expenditure in preclinical models without altering food intake or core temperature in those studies.

Identifiers

Chemical name: N⁵,N⁶-bis(2-fluorophenyl)-[1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-diamine
CAS No.: 210302-17-3
PubChem CID: 565708
Formula / MW: C₁₆H₁₀F₂N₆O • ~340.29 g·mol⁻¹

How It Works (Plain English)

Acts as a mitochondrial protonophore, dissipating the proton gradient across the inner mitochondrial membrane (mild uncoupling).
Uncoupling increases substrate oxidation and heat release in mitochondria, shifting whole-body metabolism toward higher energy expenditure in vivo models.
Unlike older uncouplers, BAM15 is reported not to depolarize the plasma membrane in vascular cells at effective concentrations (mito-selective profile in those studies).

Why Researchers Use It

To probe mechanisms of diet-induced obesity, insulin resistance, and hepatic steatosis via increased energy expenditure.
To study insulin sensitivity using clamp techniques and lipidomics/metabolomics endpoints.
To evaluate uncoupling in inflammation, sepsis, and oncology models.

Key Studies — What Was Tested, What Changed, Why It Matters

Diet-Induced Obesity & Insulin Resistance (mouse)

What was tested: Oral BAM15 in high-fat-diet mice; body composition, food intake, indirect calorimetry, lipidomics, and euglycemic clamps.
What changed: ↓ fat mass, ↑ nutrient oxidation, improved insulin sensitivity without changes in food intake or body temperature; no clinical chemistry toxicity signals reported in study.
Why it matters: Positions mitochondrial uncoupling as a lever for energy expenditure with favorable metabolic effects.

Protection Against Obesity & Glycemic Control

What was tested: BAM15-mediated uncoupling in DIO mice; glucose/lipid metabolism and adiposity outcomes.
What changed: ↓ adiposity, improved glucose tolerance/insulin sensitivity, better lipid handling.
Why it matters: Supports use in metabolic-syndrome research pipelines.

Broader Applications (reviews & translational angles)

What’s reported: Review articles summarize possible roles in lowering hepatic glucose output, anti-inflammation, and organ aging biology through mito-metabolic reprogramming.
Implication: Useful as a tool compound to dissect uncoupling across tissues and diseases (endocrine, immune, oncology).

Potential Research Applications

Metabolic Disease Models

Diet-induced obesity, hepatic steatosis, insulin resistance

Mitochondrial Bioenergetics

Respirometry (OCR), coupling/uncoupling parameters, ROS and membrane-potential assays

Inflammation & Oncology

Sepsis and macrophage activation models; tumor metabolism and proliferative fitness

Synergistic / Comparator Agents

MOTS-c or SS-31

Why pair: Contrast mitochondrial-uncoupling (BAM15) with mitochondrial-support peptides for combined bioenergetics panels.

GLP-1 / Cagrilintide (comparator)

Why compare: Appetite-centric vs energy-expenditure-centric weight-loss mechanisms.

AMPK Activators (e.g., AICAR)

Why compare: AMPK-first vs uncoupling-first metabolic remodeling.

Known Concerns (Context)

Tool-compound status: Evidence is preclinical; human PK/safety not established.
Thermogenesis/ROS: Uncoupling alters proton motive force and can affect ROS; dose-response and tissue specificity are critical.
Selectivity vs plasma membrane: Reports of minimal plasma-membrane depolarization at effective doses, but verify in your system.
General: For laboratory research use only; not for human consumption or therapeutic use.

Specifications & Handling

Form: Small-molecule solid (lot-coded)
Purity: Research-grade (HPLC/MS)
Storage: Cool, dry; protect from light/moisture

In solution: Soluble in DMSO; record solvent %, pH, and time-to-assay; minimize freeze–thaw
Labeling: Tamper-evident; research-use-only; CAS and lot displayed

Regulatory & Use Notice

Sold for laboratory research use only. Not for human consumption, medical, or veterinary use. No human-use instructions are provided. Buyer is responsible for safe handling and regulatory compliance.