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| | (E)-3-(2,3-dimethoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one Basic information |
| | (E)-3-(2,3-dimethoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one Chemical Properties |
| Melting point | 99.0-99.5 °C | | Boiling point | 454.666±45.00 °C(Press: 760.00 Torr)(predicted) | | density | 1.139±0.06 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted) | | 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. |
| WGK Germany | WGK 3 | | Storage Class | 11 - Combustible Solids | | Hazard Classifications | Aquatic Acute 1 |
| | (E)-3-(2,3-dimethoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one Usage And Synthesis |
| 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 (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 33.3μM, 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 16weeks)[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 | | References | [1] YI WANG. MD-2 as the target of a novel small molecule, L6H21, in the attenuation of LPS-induced inflammatory response and sepsis[J]. British Journal of Pharmacology, 2015, 172 17: 4391-4405. DOI:10.1111/bph.13221
[2] YALI ZHANG. Inhibition of MD2-dependent inflammation attenuates the progression of non-alcoholic fatty liver disease[J]. JOURNAL OF CELLULAR AND MOLECULAR MEDICINE, 2017, 22 2: 936-947. DOI:10.1111/jcmm.13395
[3] QILU FANG . Inhibition of myeloid differentiation factor-2 attenuates obesity-induced cardiomyopathy and fibrosis[J]. Biochimica et biophysica acta. Molecular basis of disease, 2018, 1864 1: Pages 252-262. DOI:10.1016/j.bbadis.2017.09.026
[4] XIAOXIA KONG. Chalcone Derivative L6H21 Reduces EtOH + LPS-Induced Liver Injury Through Inhibition of NLRP3 Inflammasome Activation[J]. Alcohol (Hanover, York County, Pa.), 2019, 43 8: 1662-1671. DOI:10.1111/acer.14120
[5] NATTICHA SUMNEANG . Inhibition of myeloid differentiation factor 2 attenuates cardiometabolic impairments via reducing cardiac mitochondrial dysfunction, inflammation, apoptosis and ferroptosis in prediabetic rats[J]. Biochimica et biophysica acta. Molecular basis of disease, 2022, 1868 2: Article 166301. DOI:10.1016/j.bbadis.2021.166301
[6] THURA TUN OO. L6H21 protects against cognitive impairment and brain pathologies via toll-like receptor 4–myeloid differentiation factor 2 signalling in prediabetic rats[J]. British Journal of Pharmacology, 2021, 179 6: 1220-1236. DOI:10.1111/bph.15741 |
| | (E)-3-(2,3-dimethoxyphenyl)-1-(4-methoxyphenyl)prop-2-en-1-one Preparation Products And Raw materials |
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