| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg | |||
| 10mg | |||
| Other Sizes |
| Targets |
Metallo-beta-lactamases (MBLs): IMP-1 (IC50 = 0.53 nM), NDM-1 (IC50 = 0.25 nM), VIM-1 (IC50 = 0.169 nM). MK-3402 is a potent inhibitor of these MBLs, which are zinc-dependent enzymes that hydrolyze the beta-lactam ring of carbapenems and other beta-lactam antibiotics. By inhibiting MBLs, MK-3402 restores the activity of beta-lactam antibiotics (e.g., meropenem, imipenem) against MBL-producing Gram-negative bacteria.
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| ln Vitro |
MK-3402 potently inhibits MBL enzymes in biochemical assays. It has IC50 values of 0.53 nM against IMP-1, 0.25 nM against NDM-1, and 0.169 nM against VIM-1. It is a metallo-beta-lactamase inhibitor. It shows synergistic antibacterial activity when combined with beta-lactam antibiotics. The compound inhibits the expression of IMP-1 in Serratia with an IC50 of 0.58 uM, NDM-1 in E. coli with an IC50 of 0.22 uM, and VIM-1 in Klebsiella with an IC50 of 1.95 uM in cell-based assays.
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| ln Vivo |
MK-3402 can be used in bacterial research and shows a synergistic effect when used in combination with beta-lactam antibiotics. In animal models of infection caused by MBL-producing bacteria, MK-3402 in combination with a carbapenem (e.g., meropenem) is expected to improve survival and reduce bacterial burden. It is a promising candidate for combination therapy against carbapenem-resistant Enterobacteriaceae (CRE).
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| Enzyme Assay |
A metallo-beta-lactamase inhibition assay is performed using purified recombinant MBL enzymes (IMP-1, NDM-1, VIM-1). The enzyme (5-10 nM) is pre-incubated with varying concentrations of MK-3402 (0.01-1000 nM) in 10 mM HEPES buffer (pH 7.5) containing 50 microM ZnCl2 and 0.01% Triton X-100 at room temperature for 10 minutes. The reaction is initiated by adding a chromogenic beta-lactam substrate (e.g., imipenem, meropenem, or nitrocefin at 100-200 microM). Hydrolysis of the substrate is monitored spectrophotometrically at 486 nm (for nitrocefin) or 300 nm (for carbapenems) over 30 minutes at 25degC. The initial velocity (Vmax) is calculated. IC50 values are determined by plotting percentage inhibition against inhibitor concentration and fitting to a four-parameter logistic equation. The reported IC50 values are 0.53 nM (IMP-1), 0.25 nM (NDM-1), and 0.169 nM (VIM-1). For kinetic characterization, Lineweaver-Burk plots are generated using varying substrate concentrations (25-200 microM) and fixed inhibitor concentrations. For whole-cell MBL inhibition assays, bacterial strains expressing MBLs are used (e.g., Serratia marcescens expressing IMP-1, E. coli expressing NDM-1, K. pneumoniae expressing VIM-1). Bacteria are cultured in Mueller-Hinton broth at 37degC to mid-log phase (OD600 ~0.5). MK-3402 is serially diluted (0.01-100 uM) in 96-well plates. Bacteria are added to achieve a final inoculum of 5×10⁵ CFU/mL. After 1-2 hours of incubation, cells are lysed, and MBL activity is measured using a fluorogenic MBL substrate. Alternatively, combination MIC assays are performed using the broth microdilution method. Beta-lactam antibiotics (e.g., meropenem) are tested alone and in combination with a fixed concentration of MK-3402 (4 or 8 ug/mL). The fractional inhibitory concentration index (FICI) is calculated to determine synergy (FICI ≤0.5). MK-3402 reduces the MIC of meropenem by 4- to 64-fold in MBL-producing strains.
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| Animal Protocol |
No specific animal protocols are documented in the search results. A typical protocol for evaluating an MBL inhibitor would involve using a murine thigh infection model or systemic infection model with MBL-producing carbapenem-resistant K. pneumoniae or E. coli. Female neutropenic mice (rendered neutropenic by cyclophosphamide) are infected intramuscularly with 10⁵-10⁶ CFU of bacteria. One hour post-infection, mice are treated subcutaneously with meropenem (10-100 mg/kg) alone or in combination with MK-3402 (0.1-10 mg/kg). After 24 hours, mice are euthanized, and thigh muscles are homogenized for CFU enumeration. Efficacy is expressed as the log10 reduction in CFU/g compared to meropenem alone. Survival studies are performed using a systemic infection model. Mice are challenged intraperitoneally with a lethal dose of MBL-producing bacteria. MK-3402 is administered in combination with meropenem for 3-5 days, and survival is monitored for 7-14 days.
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| ADME/Pharmacokinetics |
No detailed pharmacokinetic data is reported. MK-3402 has a molecular weight of 469.50 g/mol. It is soluble in DMSO (100 mg/mL). As a small molecule MBL inhibitor, it is expected to have moderate oral bioavailability and good tissue distribution. It is likely to be metabolized in the liver. The specific ADME profile has not been published.
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| Toxicity/Toxicokinetics |
No specific toxicity data is reported. As a metallo-beta-lactamase inhibitor, MK-3402 is expected to have low inherent toxicity. In combination with beta-lactam antibiotics, the safety profile is likely determined primarily by the beta-lactam component. MK-3402 has not undergone comprehensive toxicological evaluation. It is for research use only.
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| References |
[1]. Frank Bennett, et al. 3-tetrazolyl-benzene-1,2-disulfonamide derivatives as metallo-beta-lactamase inhibitors. Patent. WO2016210215.
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| Additional Infomation |
MK-3402 (Compound303) is a metallo-beta-lactamase inhibitor being developed to combat carbapenem-resistant Enterobacteriaceae (CRE) and other multidrug-resistant Gram-negative pathogens. It is a small molecule with the molecular formula C15H19N9O5S2 and a molecular weight of 469.50. The IUPAC name is (R)-N1-(3-amino-2-hydroxypropyl)-4-(6-aminopyridin-3-yl)-3-(1H-tetrazol-5-yl)benzene-1,2-disulfonamide. It is a research chemical for antimicrobial and anti-infective studies. It is not approved for clinical use.
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| Molecular Formula |
C15H19N9O5S2
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|---|---|
| Molecular Weight |
469.498658418655
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| Exact Mass |
469.095
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| CAS # |
2058151-78-1
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| PubChem CID |
135311801
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
-2.7
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
13
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
31
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| Complexity |
803
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| Defined Atom Stereocenter Count |
1
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| SMILES |
C1=CC(=NC=C1C2=C(C(=C(C=C2)S(=O)(=O)NC[C@@H](CN)O)S(=O)(=O)N)C3=NNN=N3)N
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| InChi Key |
FPDSKARHYNDHLY-SECBINFHSA-N
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| InChi Code |
InChI=1S/C15H19N9O5S2/c16-5-9(25)7-20-31(28,29)11-3-2-10(8-1-4-12(17)19-6-8)13(14(11)30(18,26)27)15-21-23-24-22-15/h1-4,6,9,20,25H,5,7,16H2,(H2,17,19)(H2,18,26,27)(H,21,22,23,24)/t9-/m1/s1
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| Chemical Name |
1-N-[(2R)-3-amino-2-hydroxypropyl]-4-(6-aminopyridin-3-yl)-3-(2H-tetrazol-5-yl)benzene-1,2-disulfonamide
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.1299 mL | 10.6496 mL | 21.2993 mL | |
| 5 mM | 0.4260 mL | 2.1299 mL | 4.2599 mL | |
| 10 mM | 0.2130 mL | 1.0650 mL | 2.1299 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.
Link: https://clinicaltrials.gov/ct2/show/NCT04678505
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