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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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MAC-545496 is novel and potent inhibitor of GraR (glycopeptide-resistance-associated protein R) with nanomolar activity. MAC-545496 could reverse β-lactam resistance in the community-acquired MRSA USA300 strain. MAC-545496 is an antivirulence agent alone; it attenuates MRSA virulence in Galleria mellonella larvae. MAC-545496 inhibits biofilm formation and abrogates intracellular survival in macrophages. Mechanistic characterization revealed MAC-545496 to be a nanomolar inhibitor of GraR, a regulator that responds to cell-envelope stress and is an important virulence factor and determinant of antibiotic resistance. MAC-545496 has value as a research tool to probe the GraXRS regulatory system and as an antibacterial lead series of a mechanism to combat drug-resistant Staphylococcal infections.
| Targets |
Glycopeptide-resistance-associated protein R (GraR)
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|---|---|
| ln Vitro |
With concentrations as low as 0.03 µg/mL (~75 nM), MAC-545496 potently synergizes with Cefuroxime, lowering the β-lactam MIC against S. aureus USA300 from 512 to 8 µg/mL. Additionally, MAC545496 works in concert with Oxacillin and Cefuroxime to combat a group of ten clinical isolates of S. aureus. Furthermore, to varying degrees, MAC-545496 enhances the efficacy of Cefuroxime against USA100, USA400, and USA500 strains that are currently in circulation, with the exception of CMRSA4, an isolate of USA200/EMRSA16. Additionally, MAC-545496 works in concert with polymyxin B and colistin, two antimicrobial peptides.The concentration-dependent inhibition of mprF expression is demonstrated by MAC-545496; its IC50 value is 0.0376 µg/mL.In the wild type, MAC-545496 similarly suppresses citrate-induced biofilm formation in a concentration-dependent manner[1].
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| ln Vivo |
When used as a monotherapy, MAC-545496 effectively treats MRSA-infected Galleria mellonella larvae in vivo. The higher survival rate of the drug-treated larvae in comparison to the infected untreated ones is indicative of MAC-545496 activity. This was consistent with the observation that S. aureus was killed in the hemolymph of the larvae based on concentration when the CFUs were extracted from the hemolymph 200 minutes post-infection. Treatment with MAC-545496 for S. aureus-infected larvae took place 30 minutes after infection, simulating the acquisition of bacterial infection prior to starting antimicrobial therapy [1].
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| References |
| Molecular Formula |
C18H18CLN5O3S
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|---|---|
| Molecular Weight |
419.885221004486
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| Exact Mass |
419.081
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| Elemental Analysis |
C, 51.49; H, 4.32; Cl, 8.44; N, 16.68; O, 11.43; S, 7.64
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| CAS # |
838810-96-1
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| Related CAS # |
838810-96-1;MAC-545496 HCl;
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| PubChem CID |
2983566
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| Appearance |
Solid powder
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| LogP |
4.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
28
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| Complexity |
584
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
AFOKREIUUQFDNW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C18H18ClN5O3S/c19-13-5-7-16(20-11-13)21-18(28)22-17(25)12-4-6-14(15(10-12)24(26)27)23-8-2-1-3-9-23/h4-7,10-11H,1-3,8-9H2,(H2,20,21,22,25,28)
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| Chemical Name |
N-((5-chloropyridin-2-yl)carbamothioyl)-3-nitro-4-(piperidin-1-yl)benzamide
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| Synonyms |
MAC-545496; MAC 545496; MAC545496;
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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 : ~250 mg/mL (~595.39 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 | 2.3816 mL | 11.9079 mL | 23.8158 mL | |
| 5 mM | 0.4763 mL | 2.3816 mL | 4.7632 mL | |
| 10 mM | 0.2382 mL | 1.1908 mL | 2.3816 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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