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| 1mg |
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| 100mg |
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| Targets |
M4284 targets FimH, a mannose-binding adhesin located at the tip of type 1 pili on uropathogenic Escherichia coli (UPEC). FimH mediates bacterial adhesion to mannosylated glycoproteins on the urothelial surface, a critical step in the establishment of urinary tract infections. By antagonizing FimH, M4284 prevents bacterial adhesion and colonization.
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| ln Vitro |
In vitro, M4284 is a selective and orally active FimH antagonist. It has activities against different UPEC strains responsible for urinary tract infections. The compound's ability to inhibit bacterial adhesion makes it a valuable tool for studying the pathogenesis of UTIs and developing new therapeutic strategies.
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| ln Vivo |
In mice co-colonized with UTI89 in the intestine and bladder, M4284 (oral; 100 mg/kg; 3 doses) lowers UTI89 levels in the urinary tract and gut. Additionally, giving mice higher doses of M4284 decreased the amount of UTI89, and M4284-treated animals had fewer UPEC when therapy was stopped [1].
In vivo, M4284 is an orally active FimH antagonist with activity against UPEC in different host genetic backgrounds and intestinal microbial community backgrounds. As an orally bioavailable compound, it can be administered to animal models of urinary tract infections. Its ability to prevent bacterial adhesion and colonization translates to in vivo efficacy in reducing UTI severity and recurrence. |
| Enzyme Assay |
In vitro assays for M4284 typically involve measuring its inhibition of FimH-mediated bacterial adhesion. UPEC strains are incubated with increasing concentrations of the compound and then allowed to adhere to mannosylated surfaces or urothelial cells. Bacterial adhesion is measured by colony counting or fluorescence. IC50 values are calculated from dose-response curves. The compound's selectivity for FimH over other adhesins can be assessed.
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| Cell Assay |
For in vitro cell-based assays, urothelial cells are cultured and treated with M4284 at various concentrations. UPEC strains are added to the cells, and bacterial adhesion is measured by colony counting or fluorescence microscopy. The compound's ability to prevent bacterial invasion and intracellular bacterial community formation can be assessed. Cell viability is assessed by standard assays.
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| Animal Protocol |
Animal/Disease Models: C3H/HeN mice[1].
Doses: 100 mg/kg Route of Administration: Oral; single dose. Experimental Results: Active against different UPEC strains in different host genetic backgrounds and gut microbiome environments. In vivo animal studies with M4284 are conducted in mouse models of urinary tract infections. Mice are infected with UPEC strains via transurethral inoculation. M4284 is administered orally at doses determined from pharmacokinetic studies. Bacterial burden in the bladder and kidneys is measured by colony counting. The compound's efficacy in preventing UTI and reducing bacterial colonization has been demonstrated. |
| ADME/Pharmacokinetics |
M4284 (CAS: 1373346-85-0) has a molecular weight of 460.48 g/mol and a molecular formula of C23H28N2O8. Chemical name: N3,N3',5-trimethyl-4'-{[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxy}-[1,1'-biphenyl]-3,5-dicarboxamide. Solubility: ≥51.6 mg/mL in DMSO. Storage: powder at -20°C.
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| Toxicity/Toxicokinetics |
M4284 is a research compound and is not approved for human therapeutic use. In preclinical studies, it has shown a manageable safety profile. As a FimH antagonist, it targets bacterial adhesion without directly killing bacteria, which may reduce the selective pressure for antibiotic resistance. Standard laboratory safety precautions should be followed when handling the compound.
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| References |
[1]. Schaeffer EM, et al.Selective Depletion of Uropathogenic E. coli from the Gut by a FimH Antagonist.SelectivJ Urol. 2018 Apr;199(4):874-875.
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| Additional Infomation |
M4284 is a selective and orally active biphenyl mannoside FimH antagonist. It exhibits activity against various uropathogenic Escherichia coli (UPEC) strains responsible for urinary tract infections. It has a molecular weight of 460.48 g/mol and a molecular formula of C23H28N2O8. It is not FDA-approved and is intended for research use only.
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| Molecular Formula |
C₂₃H₂₈N₂O₈
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|---|---|
| Molecular Weight |
460.48
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| Exact Mass |
460.184
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| CAS # |
1373346-85-0
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| PubChem CID |
57413592
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| Appearance |
Off-white to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
733.6±60.0 °C at 760 mmHg
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| Flash Point |
397.5±32.9 °C
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| Vapour Pressure |
0.0±2.5 mmHg at 25°C
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| Index of Refraction |
1.618
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| LogP |
-0.89
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| Hydrogen Bond Donor Count |
6
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
33
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| Complexity |
655
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| Defined Atom Stereocenter Count |
5
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| SMILES |
O1[C@@]([H])([C@]([H])([C@]([H])([C@@]([H])([C@@]1([H])C([H])([H])O[H])O[H])O[H])O[H])OC1C([H])=C([H])C(C2C([H])=C(C(N([H])C([H])([H])[H])=O)C([H])=C(C(N([H])C([H])([H])[H])=O)C=2[H])=C([H])C=1C([H])([H])[H]
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| InChi Key |
CPNXCPWXQQMNFG-WCZGSDDISA-N
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| InChi Code |
InChI=1S/C23H28N2O8/c1-11-6-12(13-7-14(21(30)24-2)9-15(8-13)22(31)25-3)4-5-16(11)32-23-20(29)19(28)18(27)17(10-26)33-23/h4-9,17-20,23,26-29H,10H2,1-3H3,(H,24,30)(H,25,31)/t17-,18-,19+,20+,23+/m1/s1
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| Chemical Name |
1-N,3-N-dimethyl-5-[3-methyl-4-[(2R,3S,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]benzene-1,3-dicarboxamide
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| Synonyms |
M4284; M-4284
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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 : ~125 mg/mL (~271.46 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 6.25 mg/mL (13.57 mM) (saturation unknown) in 10% DMSO + 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 62.5 mg/mL clear DMSO 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: ≥ 6.25 mg/mL (13.57 mM) (saturation unknown) in 10% DMSO + 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 62.5 mg/mL clear DMSO 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.1716 mL | 10.8582 mL | 21.7165 mL | |
| 5 mM | 0.4343 mL | 2.1716 mL | 4.3433 mL | |
| 10 mM | 0.2172 mL | 1.0858 mL | 2.1716 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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