WARNING: This product is for research use only, not for human or veterinary use.
Hodoodo CAT#: H522443
CAS#: 210302-17-3
Description: BAM15 is a potent and selective mitochondrial uncoupler or protonophore. Chemical mitochondrial uncouplers are lipophilic weak acids that transport protons into the mitochondrial matrix via a pathway that is independent of ATP synthase, thereby uncoupling nutrient oxidation from ATP production. These uncouplers have potential for the treatment of diseases such as obesity, Parkinson’s disease, and aging.
Hodoodo Cat#: H522443
Name: BAM15
CAS#: 210302-17-3
Chemical Formula: C16H10F2N6O
Exact Mass: 340.09
Molecular Weight: 340.290
Elemental Analysis: C, 56.47; H, 2.96; F, 11.17; N, 24.70; O, 4.70
Synonym: BAM15; BAM-15; BAM 15.
IUPAC/Chemical Name: N5,N6-bis(2-fluorophenyl)-[1,2,5]oxadiazolo[3,4-b]pyrazine-5,6-diamine
InChi Key: OEGJBRZAJRPPHL-UHFFFAOYSA-N
InChi Code: InChI=1S/C16H10F2N6O/c17-9-5-1-3-7-11(9)19-13-14(20-12-8-4-2-6-10(12)18)22-16-15(21-13)23-25-24-16/h1-8H,(H,19,21,23)(H,20,22,24)
SMILES Code: FC1=CC=CC=C1NC2=NC3=NON=C3N=C2NC4=C(C=CC=C4)F
Appearance: Solid powder
Purity: >98% (or refer to the Certificate of Analysis)
Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.
Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).
Solubility: Soluble in DMSO, not in water
Shelf Life: >2 years if stored properly
Drug Formulation: This drug may be formulated in DMSO
Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).
HS Tariff Code: 2934.99.9001
More Info:
| Biological target: | BAM 15 is a mitochondrial protonophore uncoupler and an oxidative phosphorylation (OXPHOS) uncoupler. |
| In vitro activity: | The effects of BAM15 was measured versus FCCP on plasma membrane electrophysiology using whole cell voltage and current clamp recordings. As expected, under voltage clamp conditions at a holding potential of −70 mV, FCCP induced an inward current that was dose-dependent and associated with an increase in conductance (Figure 4A–F). In contrast, BAM15 elicited no appreciable change in current in the same cells. Under current clamp conditions, FCCP caused reversible and repeatable plasma membrane depolarization, whereas BAM15 had no effect (Figure 4G and H). The differential effects of BAM15 and FCCP on plasma membrane properties were independent of the order of uncoupler application (not shown). Furthermore, BAM15-treated cells were more viable than FCCP-treated cells when administered across a broad dosing range up to 50 μM (Suppl. Figure 6). These data indicate that BAM15 does not share the adverse plasma membrane effects that may contribute to cytotoxicity. Reference: Mol Metab. 2013 Nov 28;3(2):114-23. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24634817/ |
| In vivo activity: | To determine the efficacy and feasibility of BAM15 in vivo, 10‐week‐old male diet‐induced obese (DIO) C57BL/6J mice were randomized to 3 weeks of CTRL (60% HFD) or BAM15 (60% HFD + 0.1% w/w BAM15). Ad libitum consumption of BAM15 resulted in consumption of ~85 mg/kg/day (Fig EV2A), with peak serum concentrations of ~5 μM and a half‐life of ~3 h (Fig 4A). Further assessment revealed primary distribution into adipose tissue depots and to lesser extent, liver, heart, and kidneys (Figs 4B and EV2B). By day 9, BAM15 animals displayed reduced body weight relative to control (Figs 4C and EV2C, and EV3A), an effect that persisted throughout the remainder of the treatment period. BAM15 did not affect daily (Fig EV2D and E) or cumulative food intake until day 20 (Fig 4D), at which point a mean difference in body weight of 7.5 g was observed. Neither acute intraperitoneal injection (Fig 4E) of BAM15 nor chronic oral administration (Figs 4F and EV2F) altered body temperature. Furthermore, acute oral administration of BAM15 did not alter tail heat dissipation (Fig EV2G and H). Unlike CTRL, which gained both fat and lean mass during the treatment period, BAM15 animals displayed reduced fat mass with no change in lean mass compared with baseline (Fig 4G and H). The reductions in fat mass were consistent with marked reductions in gonadal white adipose tissue (gWAT), inguinal WAT (iWAT), retroperitoneal WAT (rpWAT), and brown adipose tissue (BAT) depot weights (Fig EV3). However, there were no differences in muscle depots, such as the mixed gastrocnemius or heart (Fig EV3). In addition to adipose depots, liver weight was reduced in BAM15‐treated animals (Fig EV3), along with fasting plasma glucose and insulin (Fig 4I and J). Given the reductions in fasting glucose and insulin, glycemic control was then assessed by intraperitoneal glucose tolerance testing (IPGTT). It was observed that glucose clearance was improved in BAM15 animals relative to CTRL (Figs 4K and L and EV2I). To determine whether alterations in energy expenditure explained the reductions in body weight and adiposity, animals were placed in a metabolic chamber and examined over a 7‐day period. Oxygen consumption and total daily energy expenditure were increased (Fig 4M and N), whereas the respiratory exchange ratio (RER) was decreased (Fig 4O) in BAM15‐treated animals. Notably, the daily effect on energy expenditure was driven by changes in dark phase expenditure and consumption. In addition to energy expenditure, BAM15 preserved locomotor function, which decreased from baseline in CTRL animals (Fig EV2J and K). Cumulative water consumption was unaffected by BAM15 (Fig EV2L). To confirm that the improvements in weight regulation were attributable to increased energy expenditure, fecal lipid content was measured and no differences between groups was observed (Fig 4P). Taken together, these data suggest that BAM15 protects against diet‐induced obesity and improves glycemic control by increasing energy expenditure and reducing adiposity. Reference: EMBO Mol Med. 2020 Jul 7;12(7):e12088. https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/32519812/ |
| Solvent | Max Conc. mg/mL | Max Conc. mM | |
|---|---|---|---|
| Solubility | |||
| DMSO | 20.0 | 58.80 |
The following data is based on the product molecular weight 340.29 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|---|---|---|
| 1 mM | 1.15 mL | 5.76 mL | 11.51 mL |
| 5 mM | 0.23 mL | 1.15 mL | 2.3 mL |
| 10 mM | 0.12 mL | 0.58 mL | 1.15 mL |
| 50 mM | 0.02 mL | 0.12 mL | 0.23 mL |
| Formulation protocol: | |
| In vitro protocol: | 1. Kenwood BM, Weaver JL, Bajwa A, Poon IK, Byrne FL, Murrow BA, Calderone JA, Huang L, Divakaruni AS, Tomsig JL, Okabe K, Lo RH, Cameron Coleman G, Columbus L, Yan Z, Saucerman JJ, Smith JS, Holmes JW, Lynch KR, Ravichandran KS, Uchiyama S, Santos WL, Rogers GW, Okusa MD, Bayliss DA, Hoehn KL. Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane. Mol Metab. 2013 Nov 28;3(2):114-23. doi: 10.1016/j.molmet.2013.11.005. PMID: 24634817; PMCID: PMC3953706. 2. Axelrod CL, King WT, Davuluri G, Noland RC, Hall J, Hull M, Dantas WS, Zunica ER, Alexopoulos SJ, Hoehn KL, Langohr I, Stadler K, Doyle H, Schmidt E, Nieuwoudt S, Fitzgerald K, Pergola K, Fujioka H, Mey JT, Fealy C, Mulya A, Beyl R, Hoppel CL, Kirwan JP. BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control. EMBO Mol Med. 2020 Jul 7;12(7):e12088. doi: 10.15252/emmm.202012088. Epub 2020 Jun 10. PMID: 32519812; PMCID: PMC7338798. |
| In vivo protocol: | 1. Kenwood BM, Weaver JL, Bajwa A, Poon IK, Byrne FL, Murrow BA, Calderone JA, Huang L, Divakaruni AS, Tomsig JL, Okabe K, Lo RH, Cameron Coleman G, Columbus L, Yan Z, Saucerman JJ, Smith JS, Holmes JW, Lynch KR, Ravichandran KS, Uchiyama S, Santos WL, Rogers GW, Okusa MD, Bayliss DA, Hoehn KL. Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane. Mol Metab. 2013 Nov 28;3(2):114-23. doi: 10.1016/j.molmet.2013.11.005. PMID: 24634817; PMCID: PMC3953706. 2. Axelrod CL, King WT, Davuluri G, Noland RC, Hall J, Hull M, Dantas WS, Zunica ER, Alexopoulos SJ, Hoehn KL, Langohr I, Stadler K, Doyle H, Schmidt E, Nieuwoudt S, Fitzgerald K, Pergola K, Fujioka H, Mey JT, Fealy C, Mulya A, Beyl R, Hoppel CL, Kirwan JP. BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control. EMBO Mol Med. 2020 Jul 7;12(7):e12088. doi: 10.15252/emmm.202012088. Epub 2020 Jun 10. PMID: 32519812; PMCID: PMC7338798. |
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