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BM-212

Alias: BM-212; BM 212; BM212.
Cat No.:V12875 Purity: ≥98%
BM-212 is a potent antimycobacterial agent and MmpL3 inhibitor.
BM-212
BM-212 Chemical Structure CAS No.: 146204-42-4
Product category: Bacterial
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product Description
BM-212 is a potent antimycobacterial agent and MmpL3 inhibitor. BM-212 was shown to possess strong inhibitory activity against both Mycobacterium tuberculosis and some nontuberculosis mycobacteria. BM212 was inhibitory to drug-resistant mycobacteria and also exerted bactericidal activity against intracellular bacilli residing in the U937 human histiocytic lymphoma cell line.
BM-212 (CAS#: 146204-42-4) is a potent antimycobacterial agent and a member of the 1,5-diarylpyrrole class of compounds. Its molecular formula is C23H25Cl2N3 and its molecular weight is 414.37 g/mol. BM-212 is a potent inhibitor of MmpL3, a mycolic acid transporter essential for Mycobacterium tuberculosis viability. It exhibits strong inhibitory activity against both Mycobacterium tuberculosis and some nontuberculosis mycobacteria, including drug-resistant strains.
Biological Activity I Assay Protocols (From Reference)
Targets
M. tuberculosis
BM-212 primarily targets MmpL3, a transmembrane protein that functions as a mycolic acid transporter in mycobacteria. MmpL3 is essential for the transport of mycolic acids, key components of the mycobacterial cell wall. By inhibiting MmpL3, BM-212 disrupts mycolic acid transport and cell wall integrity, leading to bacterial cell death. This mechanism is distinct from other antitubercular agents, making BM-212 effective against drug-resistant strains.
ln Vitro
At 2 μg/mL and 8 μg/mL, BM212 completely destroys the hydrophobic nanodomains seen on S cells but has no discernible effect on R cells, causing significant structural changes in the M. abscessus CIP104536T S and R variants[3].
Mycobacterium avium's activity in U937 cells is inhibited by BM212 (0.5–10 μg/mL, 7 days) in a dose-dependent manner, with a MIC of 0.5 μg/mL and 100% inhibition beginning at a concentration of 1 μg/mL[4].
In vitro, BM-212 inhibits the growth of laboratory and clinical isolates of M. tuberculosis with MICs of 0.7-1.5 µg/ml, including strains resistant to ethambutol, isoniazid, rifampicin, and rifabutin. It also exerts bactericidal activity against intracellular bacilli residing in the U937 human histiocytic lymphoma cell line. At 2 µg/mL and 8 µg/mL, BM-212 completely destroys the hydrophobic nanodomains of M. abscessus S cells. It inhibits M. avium activity in U937 cells with a MIC of 0.5 µg/mL.
ln Vivo
Specific in vivo activity data for BM-212 is not detailed in the provided search results. As a potent antimycobacterial agent with activity against drug-resistant strains, it is being investigated for its potential in treating tuberculosis and nontuberculous mycobacterial infections. Its ability to kill intracellular bacilli suggests it may be effective in vivo. Further studies are needed to characterize its in vivo efficacy, pharmacokinetics, and safety.
Enzyme Assay
The in vitro activity of BM-212 is assessed using standard antimicrobial susceptibility testing methods. The minimum inhibitory concentration (MIC) against M. tuberculosis and other mycobacteria is determined using the broth microdilution method. Serial two-fold dilutions of BM-212 are prepared in 7H9 broth. A standardized bacterial inoculum is added, and the plates are incubated at 37°C for 5-7 days. The MIC is determined as the lowest concentration that inhibits visible growth. For mechanistic studies, MmpL3 inhibition can be assessed by measuring mycolic acid transport.
Cell Assay
For cellular assays, the U937 human histiocytic lymphoma cell line is used to assess intracellular activity. Cells are infected with M. avium, and various concentrations of BM-212 (0.5-10 µg/mL) are added for 7 days. Intracellular bacterial growth is assessed by lysing cells and plating for colony counting. For mechanistic studies, the effect of BM-212 on cell wall integrity can be assessed by electron microscopy.
Animal Protocol
In vivo, BM-212 would be administered to animal models of tuberculosis or nontuberculous mycobacterial infection. The compound is formulated in a suitable vehicle and administered at various doses via oral or intraperitoneal routes. Efficacy is assessed by measuring bacterial burden in the lungs and spleen. Pharmacokinetic studies involve measuring BM-212 levels in plasma and tissues. In toxicological studies, the compound is administered at various doses, and toxicity endpoints are assessed.
ADME/Pharmacokinetics
BM-212 has a molecular weight of 414.37 g/mol and a molecular formula of C23H25Cl2N3. It has a density of 1.2±0.1 g/cm³, a boiling point of 528.3±50.0 °C, and a logP of 5.32. The compound is a solid powder and should be stored as a powder at -20°C for up to 3 years or in solvent at -80°C for up to 6 months. It is soluble in DMSO and other organic solvents.
Toxicity/Toxicokinetics
Specific toxicity data for BM-212 is not available in the provided search results. As a potent antimycobacterial agent, its safety profile is still under investigation. The compound is intended for research purposes only and is not approved for human or veterinary use. Standard laboratory safety precautions should be followed when handling the compound. Comprehensive toxicological studies are required to establish its full safety profile.
References

[1]. Bactericidal activities of the pyrrole derivative BM212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains. Antimicrob Agents Chemother. 1998 Nov;42(11):3035-7.

[2].Improved BM212 MmpL3 inhibitor analogue shows efficacy in acute murine model of tuberculosis infection. PLoS One. 2013;8(2)

[3]. Fast chemical force microscopy demonstrates that glycopeptidolipids define nanodomains of varying hydrophobicity on mycobacteria. Nanoscale Horiz. 2020 Jun 1;5(6):944-953.

[4]. Bactericidal activities of the pyrrole derivative BM212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains. Antimicrob Agents Chemother. 1998 Nov;42(11):3035-7.

Additional Infomation
BM-212 is a potent antimycobacterial agent and MmpL3 inhibitor. It is a founding lead compound of a well-characterized class of 1,5-diarylpyrrole antimycobacterial agents. BM-212 exhibits strong inhibitory activity against both M. tuberculosis and some nontuberculosis mycobacteria, including drug-resistant strains. Its unique mechanism of action makes it a promising candidate for the development of new antitubercular drugs. BM-212 is not approved for clinical use and is intended for research purposes only.
These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C23H25CL2N3
Molecular Weight
414.374
Exact Mass
413.142
Elemental Analysis
C, 66.67; H, 6.08; Cl, 17.11; N, 10.14
CAS #
146204-42-4
Related CAS #
146204-42-4;
PubChem CID
456926
Appearance
Solid powder
Density
1.2±0.1 g/cm3
Boiling Point
528.3±50.0 °C at 760 mmHg
Flash Point
273.3±30.1 °C
Vapour Pressure
0.0±1.4 mmHg at 25°C
Index of Refraction
1.622
LogP
5.32
Hydrogen Bond Donor Count
0
Hydrogen Bond Acceptor Count
2
Rotatable Bond Count
4
Heavy Atom Count
28
Complexity
480
Defined Atom Stereocenter Count
0
SMILES
CN1CCN(CC2=C(C)N(C3=CC=C(Cl)C=C3)C(C4=CC=C(Cl)C=C4)=C2)CC1
InChi Key
YWZIODCWLMCMMW-UHFFFAOYSA-N
InChi Code
InChI=1S/C23H25Cl2N3/c1-17-19(16-27-13-11-26(2)12-14-27)15-23(18-3-5-20(24)6-4-18)28(17)22-9-7-21(25)8-10-22/h3-10,15H,11-14,16H2,1-2H3
Chemical Name
1-((1,5-bis(4-chlorophenyl)-2-methyl-1H-pyrrol-3-yl)methyl)-4-methylpiperazine
Synonyms
BM-212; BM 212; BM212.
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

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
Ethanol : ~5.56 mg/mL (~13.42 mM )
DMSO : ~1 mg/mL (~2.41 mM)
Solubility (In Vivo)
Solubility in Formulation 1: ≥ 0.56 mg/mL (1.35 mM) (saturation unknown) in 10% EtOH + 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 5.6 mg/mL clear EtOH 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: ≥ 0.56 mg/mL (1.35 mM) (saturation unknown) in 10% EtOH + 90% (20% SBE-β-CD in 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 5.6 mg/mL clear EtOH stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

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Solubility in Formulation 3: ≥ 0.56 mg/mL (1.35 mM) (saturation unknown) in 10% EtOH + 90% Corn Oil (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 5.6 mg/mL clear EtOH stock solution to 900 μL of corn oil and mix well.


Solubility in Formulation 4: 10% EtOH+40% PEG300+5% Tween-80+45% Saline: ≥ 0.56 mg/mL (1.35 mM)

 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.4133 mL 12.0665 mL 24.1330 mL
5 mM 0.4827 mL 2.4133 mL 4.8266 mL
10 mM 0.2413 mL 1.2067 mL 2.4133 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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What is the mass of compound required to make a 10 mM stock solution in 5 ml of DMSO given that the molecular weight of the compound is 350.26 g/mol?
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What volume of a given 10 mM stock solution is required to make 25 ml of a 25 μM solution?
Using the equation C1V1 = C2V2, where C1=10 mM, C2=25 μM, V2=25 ml and V1 is the unknown:
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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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In vivo Formulation Calculator (Clear solution)
Step 1: Enter information below (Recommended: An additional animal to make allowance for loss during the experiment)
Step 2: Enter in vivo formulation (This is only a calculator, not the exact formulation for a specific product. Please contact us first if there is no in vivo formulation in the solubility section.)
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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.

Biological Data
  • Chemical structure of BM212 [1,5-diaryl-2-methyl-3-(4-methylpiperazin-1-yl)-methyl-pyrrole].[1].Bactericidal activities of the pyrrole derivative BM212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains. Antimicrob Agents Chemother. 1998 Nov;42(11):3035-7.
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