L6H21

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

L6H21 是 Chalcone (HY-121054) 衍生物，是一种口服有效的特异性骨髓分化蛋白 (MD-2) 抑制剂。L6H21 高亲和力地直接与 MD-2 蛋白结合，KD 值为 33.3?μM，阻断 LPS-TLR4/MD-2 复合物形成。L6H21 抑制 LPS 诱导的 RAW264.7 巨噬细胞中 TNF-α 和IL-6 的表达，IC50 分别为 6.58 和 8.59 μM。L6H21 可用于酒精性肝病、代谢紊乱和神经炎症的研究。

L6H21, a Chalcone (HY-121054) derivative, is an orally active, potent and specific myeloid differentiation 2 (MD-2) inhibitor. L6H21 directly binds to MD-2 protein with a high affinity and low KD value of 33.3?μM, blocking the formation of the LPS-TLR4/MD-2 complex. L6H21 inhibits LPS-induced expression of TNF-α andIL-6 in RAW264.7 macrophages, with IC50 values of 6.58 and 8.59 μM, respectively. L6H21 can be used for alcoholic liver disease, metabolic disturbance and neuroinflammation research.

L6H21 (10 μM, 2 h) inhibits EtOH + LPS-induced apoptosis and mitochondrial damage in RAW264.7 cells.L6H21 (10 μM, 2 h) attenuates EtOH + LPS-induced ROS formation and TLR4–NF-κB activation, and decreases NLRP3 inflammasome activation. Apoptosis AnalysisCell Line:RAW264.7 cells (mouse macrophage cell line)Concentration:10 μMIncubation Time:2 hoursResult:Markedly decreased apoptotic cell numbers; completely inhibited EtOH + LPS-induced increase in Bax/Bcl-2; markedly decreased EtOH + LPS-induced elevation in cleaved caspase-3 protein. Western Blot Analysis Cell Line:RAW264.7 cells (mouse macrophage cell line)Concentration:10 μM Incubation Time:2 hours Result:Reduced EtOH + LPS-induced TLR4–NF-κB signaling; completely inhibited the increase in TLR4 and NF-κB p65 nuclear level induced by EtOH and LPS. Attenuated EtOH + LPS-induced expression of NLRP3 inflammasome; inhibited the elevated NLRP3 and IL-1β protein expression; decreased the expression of p20, an active form of caspase-1.Cell Viability Assay Cell Line:RAW264.7 cells (mouse macrophage cell line) Concentration:10 and 20 μM Incubation Time:2 hours Result:The loss of cell viability by EtOH + LPS was prevented by L6H21 pretreatment. Slightly decreased cell viability a higher dose of 20 μM.

L6H21 (10 mg/kg, Oral gavage, daily) effectively inhibits EtOH + LPS-induced hepatic fat accumulation, hepatic steatosis and liver injury. L6H21 (0-40 mg/kg, Orally, daily for 4 weeks) attenuates metabolic disturbance, restores cognition and attenuates brain pathologies dose and time-dependently in HFD-fed rats, and shows neuroprotective effect in a model of prediabetes.Animal Model:Male C57BL6 mice (8-10 weeks old, n = 36, 8 mice in each group, 25-30 g, with EtOH and LPS)Dosage:10 mg/kg Administration:Oral gavage, daily, before EtOH feedingResult:Decreased hepatic triglyceride (TG) concentration, markedly decreased serum alanine transaminase (ALT) and aspartate transaminase (AST) levels; Significantly decreased inflammation in liver tissue induced by EtOH + LPS.Animal Model:Male Wistar rats (6-7 weeks old, 250 g, a normal diet (ND) (n=8) or a high-fat diet (HFD) (n=104) for 16?weeks) Dosage:0, 10, 20, and 40 mg/kg Administration:Orally, daily for 1, 2 or 4 weeks Result:Ameliorated brain mitochondrial dysfunction in HFD-fed rats at 2-week administration time point; improved brain mitochondrial function in a dose-dependent manner for 4 weeks. Reduced hippocampal apoptosis in prediabetes for 4 weeks. Attenuated the reduction of dendritic spine volume and density for 4 weeks. Preserved microglial morphology in a dose-dependent manner.

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Apoptosis

NF-κB

NF-κB | TLR | TNF

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24533-47-9

298.33

C18H18O4

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 100 mg/mL (335.20 mM; 超声助溶 )

O(C)C1=C(/C=C/C(=O)C2=CC=C(OC)C=C2)C=CC=C1OC

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(-20℃)

With Ice Pack

≥ 2 years