| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg | |||
| Other Sizes |
| Targets |
EC90: 0.6 μM (AcrB)[1].
BDM91270 (compound 29) targets the AcrB subunit of the AcrAB‑TolC tripartite multidrug efflux pump in Escherichia coli. By inhibiting AcrB, BDM91270 prevents the active extrusion of various antibiotics (e.g., tetracycline, chloramphenicol, fluoroquinolones, beta‑lactams) from bacterial cells, thereby restoring the susceptibility of drug‑resistant strains to these antimicrobial agents. |
|---|---|
| ln Vitro |
In vitro, BDM91270 inhibits wild‑type E. coli AcrB with an EC90 of 0.6 microM in efflux pump inhibition assays (e.g., accumulation of a fluorescent substrate such as ethidium bromide or Nile Red). It potentiates the activity of clinically relevant antibiotics against MDR E. coli, reducing their minimum inhibitory concentrations (MICs) by 2‑ to 32‑fold depending on the antibiotic and strain.
|
| ln Vivo |
In vivo data for BDM91270 have not been published. Based on its mechanism, BDM91270 would be expected to be evaluated in mouse models of E. coli infection (e.g., urinary tract infection, peritonitis, or sepsis) in combination with an antibiotic. The efflux pump inhibitor would be co‑administered (orally or intraperitoneally) with a partner antibiotic to achieve synergy and bacterial clearance.
|
| Enzyme Assay |
For non‑cellular target engagement, E. coli membrane vesicles containing overexpressed AcrB are prepared. The accumulation of a fluorescent substrate (e.g., Nile Red, 1 microM) is measured in the presence of varying concentrations of BDM91270 (0.001-100 microM) with an energy source (e.g., NADH). Efflux pump inhibition is quantified as the reduction in substrate efflux compared to vehicle control. EC90 values are derived from dose‑response curves.
|
| Cell Assay |
E. coli strains (wild‑type and acrB‑knockout) are cultured in LB broth overnight. For efflux assays, cells are treated with BDM91270 (0.01-100 microM) for 30 min, followed by addition of a fluorescent substrate (e.g., ethidium bromide, 5 microM). Fluorescence accumulation is measured at excitation 530 nm, emission 590 nm. For MIC potentiation assays, the MIC of a test antibiotic (e.g., tetracycline or levofloxacin) is determined by broth microdilution in the absence and presence of a fixed sub‑inhibitory concentration of BDM91270 (e.g., 0.5-2 microM).
|
| Animal Protocol |
No published animal studies are available. A generic protocol for evaluating an efflux pump inhibitor in vivo would use a mouse model of systemic E. coli infection. Female BALB/c mice are infected intraperitoneally with 5 × 10⁷ CFU of an MDR E. coli strain. BDM91270 (5-50 mg/kg) and a partner antibiotic (e.g., tetracycline, 10 mg/kg) are co‑administered orally or intraperitoneally 1 h post‑infection, twice daily for 3 days. Survival and bacterial load in blood and organs (CFU/g) are measured.
|
| ADME/Pharmacokinetics |
Formal pharmacokinetic data for BDM91270 are not available. As a small molecule with moderate molecular weight (419.73 g/mol), it is expected to have moderate oral bioavailability and a short half‑life in rodents (1-4 h). Detailed PK (Cmax, Tmax, AUC, t½) would be required to support in vivo efficacy studies, but these data have not been published as of this writing.
|
| Toxicity/Toxicokinetics |
Formal toxicology studies for BDM91270 have not been conducted or published. Based on its target (bacterial efflux pump), off‑target toxicity in mammalian cells is likely minimal, as AcrB has no mammalian homolog. However, comprehensive acute and repeat‑dose toxicity studies, genotoxicity testing, and hERG safety pharmacology studies would be necessary for further drug development.
|
| References |
[1]. Compagne N, et al. Optimization of pyridylpiperazine-based inhibitors of the Escherichia coli AcrAB-TolC efflux pump. Eur J Med Chem. 2023 Jul 7;259:115630.
|
| Additional Infomation |
BDM91270 is a research‑grade tool compound for studying bacterial multidrug resistance mechanisms and developing efflux pump inhibitor‑based combination therapies. It has not entered clinical trials and is not approved for human or veterinary use. The compound is one of several AcrB inhibitors reported in the literature and serves as a lead for the development of next‑generation efflux pump inhibitors with improved potency and pharmacokinetic properties.
|
| CAS # |
2892824-11-0
|
|---|---|
| Appearance |
Off-white to light yellow solid powder
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
H2O : 50 mg/mL (119.12 mM)
DMSO : 25 mg/mL (59.56 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.96 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.96 mM) (saturation unknown) in 10% DMSO + 90% PBS (add these co-solvents sequentially from left to right, and one by one), clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
