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。
| 生物活性 | L6H21, aChalcone(HY-121054) derivative, is an orally active, potent and specificmyeloid differentiation 2(MD-2) inhibitor. L6H21 directly binds to MD-2 protein with a high affinity and lowKDvalue of 33.3 μM, blocking the formation of the LPS-TLR4/MD-2 complex. L6H21 inhibits LPS-induced expression ofTNF-αandIL-6in RAW264.7 macrophages, withIC50values of 6.58 and 8.59 μM, respectively. L6H21 can be used for alcoholic liver disease, metabolic disturbance and neuroinflammation research[1][2][3]. |
| IC50& Target | IL-6 8.59 μM (IC50) | TLR4 | NF-κB | NLRP3 inflammasome | IL-1β | Caspase 3 | Bcl-2 | Bax |
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体外研究
(In Vitro) | L6H21 (10 μM, 2 h) inhibits EtOH + LPS-inducedapoptosisand mitochondrial damage in RAW264.7 cells[1].
L6H21 (10 μM, 2 h) attenuates EtOH + LPS-induced ROS formation and TLR4–NF-κB activation, and decreases NLRP3 inflammasome activation[1].
Apoptosis Analysis[1] | Cell Line: | RAW264.7 cells (mouse macrophage cell line) | | Concentration: | 10 μM | | Incubation Time: | 2 hours | | Result: | 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[1] | 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[1] | 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. |
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体内研究
(In Vivo) | L6H21 (10 mg/kg, Oral gavage, daily) effectively inhibits EtOH + LPS-induced hepatic fat accumulation, hepatic steatosis and liver injury[1].
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[2].
| Animal Model: | Male C57BL6 mice (8-10 weeks old, n = 36, 8 mice in each group, 25-30 g, with EtOH and LPS)[1] | | Dosage: | 10 mg/kg | | Administration: | Oral gavage, daily, before EtOH feeding | | Result: | 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)[2] | | 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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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
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