MD2-IN-1

SKU: orb1303038

Description

MD2-IN-1 is a small molecule inhibitor targeting Myeloid differentiation protein 2 (MD2), exhibiting a binding affinity (K_D) of 189 µM for recombinant human MD2. This compound is a valuable research tool for investigating TLR4/MD2 signaling pathways in both cellular and animal models of inflammation and sepsis.

Research Area

Immunology & Inflammation

Key Properties

• CAS Number: 111797-22-9
• MW: 358.39
• Purity: 99.43% (May vary between batches)
• Formula: C₂₀H₂₂O₆
• SMILES: COc1ccc(cc1OC)C(=O)\C=C\c1cc(OC)c(OC)c(OC)c1
• Target: TLR
• Solubility: DMSO:55 mg/mL (153.46 mM);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2.5 mg/mL (6.98 mM)

Bioactivity

• Target IC50:
  MD2 (recombinant human):189 μM (KD)
• In Vivo:
  In the LPS-treated group, the lung wet/dry weight ratio significantly exceeds that of controls, indicating LPS-induced pulmonary edema, which MD2-IN-1 treatment effectively mitigates. Additionally, MD2-IN-1 markedly lowers the elevated protein levels in BALF caused by LPS. LPS administration results in noticeable lung histopathological alterations, such as inflammatory infiltration, hemorrhage, interstitial edema, alveolar wall thickening, and lung tissue destruction, all of which are significantly improved with MD2-IN-1 treatment.
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• In Vitro:
  Pre-treatment with different doses of MD2-IN-1 dose-dependently reduces FITC-LPS binding to MD2 in cell surface membranes, with a 65% inhibition at 10 μM in terms of mean fluorescence intensity. Pretreatment with MD2-IN-1 also dose-dependently blocks LPS-induced MAPK phosphorylation in the MPMs. Compared to the vehicle, LPS alone largely increases the amount of TLR4/MD2 complex, while pretreatment with MD2-IN-1 inhibits the increase of TLR4/MD2 complex to the vehicle level. SPR analysis shows that MD2-IN-1 exhibits recognizable binding to rhMD2 protein in a dose-dependent manner, with a KD value of 189 μM, while the KD value of xanthohumol binding to MD2 is 460 μM.
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• Cell Research:
  Mouse RAW264.7 macrophages are starved for 3 h before experimentation. Cells are incubated with or without FITC-LPS (50 μg/mL) in the presence or absence of MD2-IN-1 (0.1, 1 and 10 μM) for 30 min. After incubation, macrophages are fixed with paraformaldehyde for 10 min at 4°C and washed with PBS before being analyzed by flow cytometry.
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• Animal Research:
  Male Sprague Dawley (SD) rats are randomly divided into three groups,designated "control" (5 rats,only receive the vehicle of 0.9% saline),"LPS" (7 rats,receive 5 mg/kg LPS alone) and "MD2-IN-1 (20) + LPS" (6 rats,receive both MD2-IN-1 and 5 mg/kg LPS).Prior to LPS-induced Acute lung injury (ALI),the MD2-IN-1+LPS group rats are treated intragastrically with MD2-IN-1 at a dosage of 20 mg/kg/day continuously for one week.Under ether anesthesia,all the rats are exposed their trachea and challenged with intratracheal instillation of 50 μL of LPS,while the control group challenged with intratracheal instillation of 50 μL of 0.9% saline.Rats are then euthanized with ketamine after 6 h of LPS induction.
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Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Toll-like Receptor (TLR), TLR, MD2 IN 1, MD2IN1, MD-2-IN-1, MD2-IN-1, Inhibitor, Myeloid differentiation protein 2 (MD2), inhibit

Compound Identifiers

PubChem CID

5724738