| Identification | Back Directory | [Name]
(E)-3-(2,3-dimethoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one | [CAS]
24533-47-9 | [Synonyms]
L6H21
(E)-3-(2,3-dimethoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one | [Molecular Formula]
C18H18O4 | [MOL File]
24533-47-9.mol | [Molecular Weight]
298.333 |
| Chemical Properties | Back Directory | [storage temp. ]
-20°C | [solubility ]
Soluble in DMSO (60 mg/ml) | [form ]
solid | [color ]
White | [Stability:]
Stable for 2 years from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months. |
| Hazard Information | Back Directory | [Description]
L6H21 binds to MD-2 (myeloid differentiation protein-2, Kd=33.3 μM) and blocks its interaction with TLR4 (toll-like receptor 4) in LPS-stimulated cells, inhibiting TNFα and IL-6 production.1 Attenuates disease progression in a high-fat diet (HFD) induced NASH mouse model.2 Inhibits obesity-induced cardiomyopathy and fibrosis.3 Reduces ethanol plus LPS-induced liver injury via inhibition of NLRP3 inflammasome activation.4 Provides cardioprotective effects5 and protects against cognitive impairment and brain pathologies in HFD prediabetic rats6. Cell permeable. Active in vivo. | [Uses]
L6H21, a Chalcone.html" class="link-product" target="_blank">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 and IL-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[1][2][3]. | [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. |
| [IC 50]
IL-6: 8.59 μM (IC50); TLR4; NF-κB; NLRP3 inflammasome; IL-1β; Caspase 3; Bcl-2; Bax | [storage]
-20°C | [References]
Wang et al. (2015), MD-2 as the target of a novel small molecule, L6H21, in the attenuation of LPS-induced inflammatory response and sepsis; J. Pharmacol., 172 4391
Zhang et al. (2018), Inhibition of MD1-dependent inflammation attenuates the progression of non-alcoholic fatty liver disease; Cell. Mol. Med., 22 936
Fang et al. (2018), Inhibition of myeloid differentiation factor-2 attenuates obesity-induced cardiomyopathy and fibrosis; Biophys. Acta Mol. Basis Dis., 1864 252
Kong et al. (2019), Chalcone Derivative L6H21 Reduces EtOH + LPS-Induced Liver Injury Through Inhibition of NLRP3 Inflammasome Activation; Alcohol Clin. Exp. Res., 43 1662
Sumneang et al. (2022), Inhibition of myeloid differentiation factor-2 attenuates cardiometabolic impairments via reducing cardiac mitochondrial dysfunction, inflammation, apoptosis and ferroptosis in prediabetic rats; Biophys. Acta Mol. Basis Dis., 1868 166301
Oo et al. (2021), L6H21 protects against cognitive impairment and brain pathologies via toll-like receptor 4-myeloid differentiation factor 2 signalling in prediabetic rats; J. Pharmacol., doi:10.1111/bph.15741 Epub ahead of print |
|
| Company Name: |
Merck KGaA
|
| Tel: |
21-20338288 |
| Website: |
www.sigmaaldrich.cn |
|