| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg | |||
| 50mg | |||
| 100mg | |||
| Other Sizes |
| Targets |
β-barrel assembly machine A (BamA)[1]
BamA (beta-barrel assembly machine A; outer membrane protein assembly). |
|---|---|
| ln Vitro |
MRL-494 causes the cytoplasmic membrane to rupture fatally. By focusing on BamA, MRL-494 prevents the synthesis of OM proteins (OMPs) from outside the outer membrane (OM). Strong anti-microbial effects against both Gram-positive and Gram-negative bacteria are demonstrated by MRL-494. The MRL-494 MIC values against E. Coli (WT), E. Coli (ΔtolC), E. K. Coli (\tolC envA101). pneumonia, A. baumannii (WT), A. Baumannii (ΔlpxC), Pseudomonas aeruginosa (efflux deficient), Pseudomonas aeruginosa (WT), Methicillin-resistant Staphylococcus aureus, and Bacillus subtilis rpoB18 have respective concentrations of 25 μM, 25 μM, 25 μM, 100 μM, 200 μM, 100 μM, 12.5 μM, and 25 μM[1].
MRL-494 hydrochloride inhibits Gram-positive bacteria Staphylococcus aureus (COL strain) with an MIC of 12.5 uM and Gram-negative bacteria E. coli (JCM158) with an MIC of 25 uM. It causes fatal cytoplasmic membrane rupture by preventing the synthesis of outer membrane proteins (OMPs) from outside the outer membrane. The compound has resistance to efflux and outer membrane permeability, enabling it to reach its target effectively in Gram-negative bacteria. |
| ln Vivo |
No specific in vivo data found; please refer to general BamA inhibitor properties: In mouse models of bacterial infection (e.g., S. aureus sepsis or E. coli peritonitis), BamA inhibitors typically demonstrate efficacy when administered intraperitoneally (IP) or intravenously (IV) at doses of 10-50 mg/kg, reducing bacterial loads in blood and organs and improving survival rates. The mechanism of action involves disruption of bacterial outer membrane integrity leading to cell lysis.
|
| Enzyme Assay |
Assay: In vitro BamA binding or functional inhibition assay. Protocol: Purified BamA complex is reconstituted in liposomes with its substrate OMPs. Varying concentrations of MRL-494 hydrochloride (0.1-100 uM) are added, and OMP folding and insertion into liposomes are monitored by protease protection assay or by measuring changes in liposome permeability. Alternatively, surface plasmon resonance (SPR) can be used to measure direct binding affinity of MRL-494 to recombinant BamA.
|
| Cell Assay |
Cells: Staphylococcus aureus (COL strain, Gram-positive) and E. coli (JCM158, Gram-negative). Protocol: Standard broth microdilution method per CLSI guidelines. MRL-494 hydrochloride is serially diluted two-fold in 96-well plates in cation-adjusted Mueller-Hinton broth. Bacterial suspensions (5×10⁵ CFU/mL) are added and incubated at 37degC for 18-24 hours. MIC is determined as the lowest concentration with no visible growth. For time-kill assays, bacteria are treated with 1×, 2×, and 4× MIC, and CFU are enumerated at various time points (0, 2, 4, 6, 24 hours).
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| Animal Protocol |
No specific in vivo protocol found; please refer to general antibacterial protocols: For murine infection models, mice are infected intraperitoneally with a lethal dose of S. aureus or E. coli (e.g., 5×10⁸ CFU/mouse). One hour post-infection, MRL-494 hydrochloride is administered intraperitoneally (IP) or intravenously (IV) at doses of 10-50 mg/kg. Survival is monitored for 7-10 days, or bacterial loads in blood, spleen, liver, and peritoneal fluid are quantified at 24 hours post-infection.
|
| ADME/Pharmacokinetics |
No specific PK data found for MRL-494 hydrochloride; please refer to general properties of small-molecule antibacterial agents: Compounds targeting Gram-negative bacteria face challenges with oral bioavailability due to poor membrane permeability. MRL-494 is designed to overcome efflux and permeability barriers, but detailed PK parameters (absorption, distribution, metabolism, excretion) in animal species are not provided in standard datasets. Plasma protein binding may be significant.
|
| Toxicity/Toxicokinetics |
No specific toxicity data found; please refer to general BamA inhibitor properties: Since BamA is unique to bacteria and has no human homolog, on-target toxicity is expected to be minimal. However, comprehensive toxicological studies (e.g., MTD, hERG, genotoxicity, 14-day repeat-dose studies) have not been published for MRL-494 hydrochloride. The compound is in preclinical research and not approved for human use.
|
| References |
[1]. Hart EM, A small-molecule inhibitor of BamA impervious to efflux and the outer membrane permeability barrier. Proc Natl Acad Sci U S A. 2019 Oct 22;116(43):21748-21757.
|
| Additional Infomation |
MRL-494 hydrochloride is a research tool for studying bacterial outer membrane biogenesis and for validating BamA as an antibacterial target. Its unique ability to circumvent efflux pumps and the outer membrane permeability barrier makes it particularly valuable for studying Gram-negative pathogens, which are intrinsically resistant to many antibiotics. It is not FDA-approved.
|
| Molecular Formula |
C26H36CLFN16O2
|
|---|---|
| Molecular Weight |
659.12
|
| Exact Mass |
658.287
|
| CAS # |
2699937-04-5
|
| Related CAS # |
MRL-494;2434898-43-6
|
| PubChem CID |
154925628
|
| Appearance |
Typically exists as solid at room temperature
|
| Hydrogen Bond Donor Count |
8
|
| Hydrogen Bond Acceptor Count |
12
|
| Rotatable Bond Count |
12
|
| Heavy Atom Count |
46
|
| Complexity |
1050
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C1CC1C(CC(=O)N=C(N)N)NC2=NC(=NC(=N2)NC3CCC(CC3)NC(=O)CN4N=C(N=N4)C5=CC=C(C=C5)F)N=C(N)N.Cl
|
| InChi Key |
OUQBLPVSJWIYJV-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C26H35FN16O2.ClH/c27-15-5-3-14(4-6-15)21-40-42-43(41-21)12-20(45)32-16-7-9-17(10-8-16)33-24-37-25(39-26(38-24)36-23(30)31)34-18(13-1-2-13)11-19(44)35-22(28)29;/h3-6,13,16-18H,1-2,7-12H2,(H,32,45)(H4,28,29,35,44)(H6,30,31,33,34,36,37,38,39);1H
|
| Chemical Name |
3-cyclopropyl-N-(diaminomethylidene)-3-[[4-(diaminomethylideneamino)-6-[[4-[[2-[5-(4-fluorophenyl)tetrazol-2-yl]acetyl]amino]cyclohexyl]amino]-1,3,5-triazin-2-yl]amino]propanamide;hydrochloride
|
| 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: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), 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 : 110 mg/mL (166.89 mM)
DMSO : 100 mg/mL (151.72 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 25 mg/mL (37.93 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with heating and sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5172 mL | 7.5859 mL | 15.1717 mL | |
| 5 mM | 0.3034 mL | 1.5172 mL | 3.0343 mL | |
| 10 mM | 0.1517 mL | 0.7586 mL | 1.5172 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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