| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| Targets |
BM635 targets MmpL3, a transmembrane transporter essential for the export of mycolic acids in Mycobacterium tuberculosis. By inhibiting MmpL3, BM635 disrupts the transport of mycolic acids, leading to disruption of the mycobacterial cell wall and bacterial cell death. The compound has a MIC50 of 0.12 μM against M. tuberculosis H37Rv.
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| ln Vitro |
BM635 exhibits potent anti-mycobacterial activity with a minimum inhibitory concentration (MIC50) of 0.12 μM against M. tuberculosis H37Rv. The compound has a Tox50-MIC ratio of >100, indicating a favorable therapeutic window. It shows good microsomal stability in mice (1.4 mL/min/g).
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| ln Vivo |
BM635 exhibits strong microsomal stability in mice (1.4 mL/min/g), a Tox50:MIC ratio >100, and a powerful MIC (0.12 µM). In an acute mouse infection model, BM635 showed strong anti-tuberculosis action at various doses, with an ED99 of 49 mg/Kg (IC95%: 43–54 mg/Kg) [1]. BM635 has an in vivo half-life of one hour, which permits a moderate bioavailability (46%) and a tolerable maximum concentration (Cmax=1.62 μM). Its high lipophilicity and poor water solubility lead to a modest in vivo exposure [2].
In an acute murine infection model, BM635 exhibits potent anti-tubercular activity with an ED99 of 49 mg/kg (95% CI: 43–54 mg/kg). The compound has a half-life of approximately 1 hour in vivo, with a maximum concentration (Cmax = 1.62 μM) and moderate bioavailability (46%). Its poor aqueous solubility and high lipophilicity lead to low exposure in vivo. |
| Enzyme Assay |
For MIC determination, two-fold drug dilutions of BM635 in DMSO starting at 200 μM are prepared. Five µL of drug solutions are added to 95 µL of Middlebrook 7H9 medium. The inoculum of M. tuberculosis H37Rv is standardized to approximately 1×10⁷ CFU/mL and diluted 1:100. One hundred µL of inoculum is added to each well. Plates are incubated at 37°C for six days without shaking. Resazurin is added to assess bacterial growth, and MIC values are determined as the lowest concentration inhibiting visible growth.
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| Cell Assay |
Cellular assays are performed using M. tuberculosis H37Rv cultured in Middlebrook 7H9 broth. BM635 is tested at various concentrations (typically starting at 200 μM with two-fold dilutions). After six days of incubation at 37°C, resazurin is added, and fluorescence is measured to quantify bacterial viability. The MIC50 is calculated as the concentration inhibiting 50% of bacterial growth compared to untreated controls.
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| Animal Protocol |
In an acute murine infection model, mice are infected with M. tuberculosis and treated with BM635 at multiple doses. The compound is administered orally or intraperitoneally. Bacterial burden in lungs and spleen is determined by colony-forming unit (CFU) counts on agar plates. The ED99 (effective dose for 99% reduction in bacterial burden) is calculated from dose-response curves.
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| ADME/Pharmacokinetics |
BM635 has a half-life of approximately 1 hour in vivo, with a maximum concentration (Cmax) of 1.62 μM and moderate bioavailability of 46%. The compound exhibits good microsomal stability in mice (1.4 mL/min/g). However, its poor aqueous solubility together with high lipophilicity leads to low exposure in vivo.
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| Toxicity/Toxicokinetics |
BM635 has a Tox50-MIC ratio of >100, indicating a favorable therapeutic window with low toxicity relative to its antimicrobial activity. In animal studies, the compound is well-tolerated at doses up to the ED99.
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| References |
[1]. Poce G, et al. Improved BM212 MmpL3 inhibitor analogue shows efficacy in acute murine model of tuberculosis infection. PLoS One. 2013;8(2):e56980.
[2]. Poce G, et al. Pharmaceutical salt of BM635 with improved bioavailability. Eur J Pharm Sci. 2017 Mar 1;99:17-23 |
| Additional Infomation |
BM635 is an MmpL3 inhibitor with outstanding anti-mycobacterial activity (MIC50 = 0.12 μM against M. tuberculosis H37Rv). It exhibits potent anti-tubercular activity in an acute murine infection model with an ED99 of 49 mg/kg. The compound has a Tox50-MIC ratio of >100.
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| Molecular Formula |
C25H29FN2O
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|---|---|
| Molecular Weight |
392.508970022202
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| Exact Mass |
392.226
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| CAS # |
1493762-74-5
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| Related CAS # |
BM635 hydrochloride;2748337-90-6;BM635 mesylate;2703867-74-5
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| PubChem CID |
73953235
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
5.1
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
29
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| Complexity |
493
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1=C(C=C(N1C2=CC=C(C=C2)F)C3=CC=C(C=C3)C(C)C)CN4CCOCC4
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| InChi Key |
NEEGNYKRJDHJNX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C25H29FN2O/c1-18(2)20-4-6-21(7-5-20)25-16-22(17-27-12-14-29-15-13-27)19(3)28(25)24-10-8-23(26)9-11-24/h4-11,16,18H,12-15,17H2,1-3H3
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| Chemical Name |
4-[[1-(4-fluorophenyl)-2-methyl-5-(4-propan-2-ylphenyl)pyrrol-3-yl]methyl]morpholine
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~31 mg/mL (~78.98 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.5477 mL | 12.7385 mL | 25.4771 mL | |
| 5 mM | 0.5095 mL | 2.5477 mL | 5.0954 mL | |
| 10 mM | 0.2548 mL | 1.2739 mL | 2.5477 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.
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.
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