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MD2-IN-1

CAS No. : 111797-22-9

MCE 站：MD2-IN-1

产品活性：MD2-IN-1 是髓样分化蛋白 2 (MD2) 的抑制剂，对重组人 MD2 (rhMD2) 的 KD 值为 189 μM。

研究领域：Immunology/Inflammation

作用靶点：Toll-like Receptor (TLR)

In Vitro: Myeloid differentiation protein 2 (MD2) is a co-receptor of TLR4. Among those derivatives, MD2-IN-1 (compound 20) shows the strongest inhibitory effect on LPS-induced expression of both TNF-α and IL-6. Compare 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. 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.

In Vivo: Administration of MD2-IN-1 evidently reduces the LPS-induced increase in protein concentrations in BALF. The lung wet/dry weight ratio is markedly higher in the LPS-treated group than the control group, and MD2-IN-1 treatment reduces LPS-induced pulmonary edema. LPS also causes observable lung histopathologic changes, including areas of inflammatory infiltration, hemorrhage, interstitial edema, thickening of the alveolar wall, and lung tissue destruction. These histopathological changes are ameliorated in the MD2-IN-1 treatment group.

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