MyD88-IN-3
Based on 1 Customer Validation
MyD88-IN-3 is an orally active, selective MyD88 Inhibitor. MyD88-IN-3 specifically targets the TIR domain of MyD88 (KD = 28.5 μM), thereby preventing MyD88 self-polymerization and interaction with TLRs, which suppresses the activation of MAPK and NF-κB pathways. MyD88-IN-3 demonstrates significant anti-inflammatory efficacy and effectively mitigates Acute Lung Injury (ALI) symptoms in CLP (cecal ligation and puncture) and Lipopolysaccharides (HY-D1056) (LPS)-induced ALI models. MyD88-IN-3 can be used for the study of ALI.
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- Pureté : 99.33%
- Formule: C24H24N6O5S
- Masse moléculaire:508.55
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Stockage:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
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Activité biologique
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Chemical Information
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Solvant et solubilité
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
In Vitro
MyD88-IN-3 (Compound 3g) (1.1-30 μM) demonstrates potent anti-inflammatory effects by significantly inhibiting IL-6 secretion in the mouse macrophage J774A.1 (IC50 = 1.32 μM) and human THP-1 (IC50 = 0.75 μM ) macrophages differentiated with PMA[1].
MyD88-IN-3 (10 μM, pretreatment for 2 h, followed by co-treatment with 0.5 μg/mL LPS for 30 minutes) restores the decreased expression level of IκBα induced by LPS, significantly reduces the phosphorylation of p38, inhibits the phosphorylation of JNK, suppresses phosphorylation and nuclear translocation of p65, and inhibits LPS-induced activation of the MAPK pathway, leading to nuclear translocation of c-Jun in J774A.1 macrophage[1].
MyD88-IN-3 (5 μM, 10 μM) can inhibit MyD88 homodimerization in J774A.1[1].
MyD88-IN-3 (10 μM, 2 h) can inhibit the interaction between MyD88 and TLR4 in J774A.1[1].
MyD88-IN-3 (10 μM, 4 h) improves the thermal stability of MyD88, preserving roughly 50% of MyD88 at 64 °C[1].
MyD88-IN-3 binds efficiently to the TIR domain (KD = 28.5 μM), while exhibiting no binding affinity for the DD domain (KD = 1.32 M)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only. Further protocols information, click here.
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Cell Line:J774A.1 mouse macrophages
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Concentration:Pretreatment for 2 h, followed by co-treatment with 0.5 μg/mL LPS for 30 minutes
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Incubation Time:2 h
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Result:Restored LPS-induced IκBα degradation and inhibited p38 and JNK phosphorylation.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-t | AUC0-∞ | Vz | CL | F |
|---|---|---|---|---|---|---|---|---|---|---|
| Rat | 1 mg/kg | i.v. | 2.005 h | 0.133 h | 20470.326 ng/mL | 21742.905 ng·h/mL | 21793.761 ng·h/mL | 0.157 L/kg | 0.052 L/h/kg | / |
| Rat | 10 mg/kg | p.o. | 3.974 h | 3.333 h | 21139.044 ng/mL | 136935.065 ng·h/mL | 139481.151 ng·h/mL | 0.468 L/kg | 0.077 L/h/kg | 63 % |
In Vivo
MyD88-IN-3 (20 mg/kg, Oral gavage, pretreated 6 h) mitigates sepsis-induced ALI in C57BL/6 mice[1].
MyD88-IN-3 (20 mg/kg, Oral gavage, pretreated 30 min) Attenuated LPS-Induced ALI in C57BL/6 mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:SD rats[1]
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Dosage:500 mg/kg, 1000 mg/kg
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Administration:Oral gavage, once daily for 10 days
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Result:Induced a slight decrease in body weight in the first day, following which body weight progressively returned to levels akin to the control group, with no statistically significant differences noted.
Indicated no notable pathological alterations in the organs of mice.
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Animal Model:Male C57BL/6 mice, weighing between 18 and 22 g, after the administration of anesthesia, an abdominal incision was performed to reveal the cecum. The cecum was ligated beneath the ileocecal valve with surgical thread and subsequently punctured once with a needle. The abdominal incision was subsequently sutured closed after repositioning[1]
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Dosage:20 mg/kg
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Administration:Oral gavage, administer 6 hours before CLP surgery
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Result:Markedly diminished the lung wet/dry weight ratio, demonstrating its effectiveness in alleviating sepsis-induced lung edema.
Obstructed this cellular influx into BALF, suggesting that MyD88-IN-3 alleviates sepsis-induced pulmonary edema.
led to a significant decrease in IL-6.
Alleviated lung tissue damage, interstitial edema, pulmonary congestion, inflammatory infiltration, and thickened alveolar septa.
Significantly diminished immune cell infiltration, thereby mitigating the inflammatory response.
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Animal Model:LPS-Induced Male C57BL/6 mice, weighing between 18 and 22 g
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Dosage:20 mg/kg
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Administration:Oral gavage, administer 30 min before LPS.
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Result:Markedly diminished the lung wet/dry weight ratio, demonstrating its effectiveness in alleviating sepsis-induced lung edema.
Significantly suppressed the increase in total protein concentration and the discharge of immune cells into BALF.
Decreased spleen weight and mitigated inflammation.
Markedly reduced IL-6 levels in both bronchoalveolar lavage fluid and serum samples.
Mitigated augmented alveolar septal thickness, pulmonary congestion, inflammatory infiltration, and lung tissue degradation.
Reduced leukocyte infiltration into the alveoli.
Chemical Information
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Appearance Solid
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Masse moléculaire 508.55
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Formule C24H24N6O5S
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Color Light yellow to yellow
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SMILES
O=S(C1=CC=C(N2CCN(CC3=CC=C(C#N)C=C3)CC2)C([N+]([O-])=O)=C1)(NC4=CC=C(OC)N=C4)=O
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
Solvant et solubilité
In Vitro:
DMSO : 100 mg/mL (196.64 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
In Vivo:
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 5 mg/mL (9.83 mM); Suspended solution
This protocol yields a suspended solution of ≥ 5 mg/mL (saturation unknown). Suspended solution can be used for oral and intraperitoneal injection.
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (50.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
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%+
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+%Tween-80 + +
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%Saline +
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Protocole
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Research Protocol for Inflammation-related Diseases
The NLRP3 inflammasome is a cytosolic innate immune signaling platform that integrates priming signals and danger-signal activation to promote caspase-1 activation, maturation of IL-1β and IL-18, and gasdermin D-mediated pyroptotic cell death. The core experimental logic is to determine whether inflammatory disease phenotypes are driven by increased NLRP3 expression, ASC-containing inflammasome assembly, caspase-1 cleavage, GSDMD cleavage, and extracellular release of IL-1β/IL-18 rather than by nonspecific cell injury alone. The pathway is strongly linked to inflammation-related disease phenotypes because monosodium urate crystals activate NALP3/NLRP3 inflammasome signaling in gout-like crystal inflammation, cholesterol crystals activate NLRP3 inflammasomes in atherogenesis models, and DSS-induced intestinal inflammation has been reported to involve NLRP3 inflammasome activity. However, experimental colitis studies also show context-dependent protective effects of NLRP3 inflammasome co
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Inhalation Toxicity Study
Inhalation toxicity studies expose rodents to a controlled aerosol, vapor, gas, or smoke atmosphere and assess respiratory and systemic toxicity using exposure-atmosphere characterization, clinical observations, body and organ weights, bronchoalveolar lavage fluid, histopathology, blood chemistry, hematology, and, when included, molecular endpoints such as transcriptomics, proteomics, lipidomics, or tissue burden analysis. The primary biological readouts are airway irritation, pulmonary inflammation, cytotoxicity, altered surfactant or lipid homeostasis, impaired particle clearance, and tissue remodeling, reflected by BALF cell differentials, BALF protein, LDH, phosphatase activities, cytokines, lung weight, microscopic respiratory-tract lesions, and retained lung burden.
Pureté et documentation
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Fiche technique (278 KB)
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SDS (251 KB)
- English - EN (251 KB)
- Français - FR (251 KB)
- Deutsch - DE (251 KB)
- Norwegian - NO (251 KB)
- Español - ES (251 KB)
- Swedish - SV (251 KB)
- Italian - IT (251 KB)
- Korean - KR (251 KB)
- Portuguese - PT (251 KB)
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Instruction de manipulation (2659 KB)
Références
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.9664 mL | 9.8319 mL | 19.6638 mL | 49.1594 mL |
| 5 mM | 0.3933 mL | 1.9664 mL | 3.9328 mL | 9.8319 mL | |
| 10 mM | 0.1966 mL | 0.9832 mL | 1.9664 mL | 4.9159 mL | |
| 15 mM | 0.1311 mL | 0.6555 mL | 1.3109 mL | 3.2773 mL | |
| 20 mM | 0.0983 mL | 0.4916 mL | 0.9832 mL | 2.4580 mL | |
| 25 mM | 0.0787 mL | 0.3933 mL | 0.7866 mL | 1.9664 mL | |
| 30 mM | 0.0655 mL | 0.3277 mL | 0.6555 mL | 1.6386 mL | |
| 40 mM | 0.0492 mL | 0.2458 mL | 0.4916 mL | 1.2290 mL | |
| 50 mM | 0.0393 mL | 0.1966 mL | 0.3933 mL | 0.9832 mL | |
| 60 mM | 0.0328 mL | 0.1639 mL | 0.3277 mL | 0.8193 mL | |
| 80 mM | 0.0246 mL | 0.1229 mL | 0.2458 mL | 0.6145 mL | |
| 100 mM | 0.0197 mL | 0.0983 mL | 0.1966 mL | 0.4916 mL |
MyD88-IN-3 Related Classifications
HY-178136 Related Classifications
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