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Purity: ≥98%
MD2-IN-1, a chalcone derivative, is a novel potent and specific inhibitor of Myeloid differentiation protein 2 (MD2) with potential anti-inflammatory activity. It inhibits MD2 with a KD of 189 μM for the recombinant human MD2 (rhMD2). Acute lung injury (ALI) is a life-threatening acute inflammatory disease with limited options available for therapy. Myeloid differentiation protein 2, a co-receptor of TLR4, is absolutely required for TLR4 sense LPS, and represents an attractive target for treating severe inflammatory diseases.MD2-IN-1 contains the moiety of (E)-4-phenylbut-3-en-2-one, which is considered to be the core structure of current MD2 inhibitors. The anti-inflammatory activities of MD2-IN-1 was evaluated in MPMs. MD2-IN-1 binds to the hydrophobic pocket of MD2 via hydrogen bonds with Arg(90) and Tyr(102) residues. MD2-IN-1 also blocked the LPS-induced activation of TLR4/MD2 -downstream pro-inflammatory MAPKs/NF-κB signaling pathways. In a rat model with ALI induced by intracheal LPS instillation, administration with MD2-IN-1 exhibited significant protective effect against ALI, accompanied by the inhibition of TLR4/MD2 complex formation in lung tissues. Taken together, the results of this study suggest the specific MD2 inhibitor from chalcone derivatives is a potential candidate for treating acute inflammatory diseases.
| ln Vitro |
TLR4's coreceptor is myeloid differentiation protein 2 (MD2). Of all the derivatives, compound 20 (MD2-IN-1) had the most potent inhibitory effect on the production of TNF-α and IL-6 produced by LPS. While pretreatment with MD2-IN-1 suppressed the increase in TLR4/MD2 complexes to vehicle levels, LPS alone significantly enhanced the quantity of TLR4/MD2 complexes relative to vehicle. SPR study revealed that xanthohumol bound to MD2 with a KD value of 460 μM, whereas MD2-IN-1 bound to rhMD2 protein in a dose-dependent manner with a KD value of 189 μM. The binding of FITC-LPS to MD2 in the cell surface membrane was dose-dependently decreased by pretreatment with several dosages of MD2-IN-1, with an average fluorescence intensity inhibition of 65% at 10 μM. Additionally, pretreatment with MD2-IN-1 dose-dependently prevents MPM-induced MAPK phosphorylation caused by LPS [1].
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| ln Vivo |
The LPS-induced rise in protein concentration in BALF was considerably attenuated by administering MD2-IN-1. A treatment of MD2-IN-1 reduced LPS-induced pulmonary edema, and the lung wet/dry weight ratio in the LPS treatment group was considerably greater than in the control group. Furthermore, areas of inflammatory infiltrates, bleeding, interstitial edema, thickening of the alveolar wall, and loss of lung tissue are all visible histological changes brought on by LPS. In the group receiving MD2-IN-1 treatment, these histological alterations improved [1].
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| References |
[1]. Zhang Y, et al. Discovery of new MD2 inhibitor from chalcone derivatives with anti-inflammatory effects in LPS-induced acute lung injury. Sci Rep. 2016 Apr 27;6:25130
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| Molecular Formula |
C20H22O6
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| Molecular Weight |
358.39
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| CAS # |
111797-22-9
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| Related CAS # |
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| SMILES |
COC1=C(OC)C(OC)=CC(/C=C/C(C2=CC=C(OC)C(OC)=C2)=O)=C1
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| Chemical Name |
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
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| 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) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 3.25 mg/mL (9.07 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 32.5 mg/mL clear DMSO stock solution to 400 μL of PEG300 and mix evenly; then add 50 μL of Tween-80 to the above solution and mix evenly; then add 450 μL of 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: 3.25 mg/mL (9.07 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 32.5 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. View More
Solubility in Formulation 3: ≥ 3.25 mg/mL (9.07 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7903 mL | 13.9513 mL | 27.9026 mL | |
| 5 mM | 0.5581 mL | 2.7903 mL | 5.5805 mL | |
| 10 mM | 0.2790 mL | 1.3951 mL | 2.7903 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.
Inhibition of TNF-α and IL-6 production as indicated by chalcone derivatives.Sci Rep.2016 Apr 27;6:25130. |
Compound 20 (MD2-IN-1) is a specific inhibitor of MD2. |
Compound20(MD2-IN-1)binds with MD2 via interacting with Arg90and Tyr102. |
Effects of compound20(MD2-IN-1)on the LPS-induced activation of MAPK and NF-κB and expression of inflammatory genes.Sci Rep.2016 Apr 27;6:25130. |
Proposed model of signaling pathway involved in compound 20(MD2-IN-1) preventing LPS-induced TLR4 signaling pathway activation and acute lung injury.Sci Rep.2016 Apr 27;6:25130. |
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