LM9
LM9 is a potent, orally active MyD88 inhibitor. LM9 blocks TLR4/MyD88 binding, MyD88 homodimer formation, and TLR4/MyD88/NF-κB signaling pathway activation. LM9 prevents atherosclerosis by regulating inflammatory responses and oxidative stress in macrophages. LM9 efficiently mitigates inflammatory responses and fibrosis in obesity-induced cardiomyopathy. LM9 can be used for fibrosis and atherosclerosis research.
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- No. CAS: 2249864-11-5
- Fòrmula: C24H27N5O5S
- Peso molecular:497.57
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Chemical Information
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- Referencias
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Help & FAQs
Actividad biológica
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NF-κB |
TLR4 |
Collagen I |
Collagen IV |
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Cell Line
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Type | Value | Description | References |
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| Peritoneal macrophage | IC50 |
0.89 μM
Compound: 15d
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Antiinflammatory activity in ICR mouse primary peritoneal macrophages assessed as inhibition of LPS-induced TNFalpha production preincubated for 2 hrs followed by LPS stimulation and measured after 22 hrs by ELISA
Antiinflammatory activity in ICR mouse primary peritoneal macrophages assessed as inhibition of LPS-induced TNFalpha production preincubated for 2 hrs followed by LPS stimulation and measured after 22 hrs by ELISA
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[PMID: 30342423] |
LM9 (5-10 μM; 1 h pretreat) attenuates Palmitic Acid (PA) (HY-N0830)-induced inflammation in mouse peritoneal macrophages by reducing proinflammatory cytokine production and ICAM-1 expression[1].
LM9 (5-10 μM; 1 h pretreat) suppresses PA-induced inflammation and NF-κB signaling activation in H9C2 cells[1].
LM9 (5-10 μM) inhibits PA-induced TLR4/MyD88 binding and MyD88 homodimer formation in HEK293T cells[1].
LM9 (5-10 μM; 1 h pretreat) alleviates PA-induced lipid accumulation and fibrosis in H9C2 cells, decreasing collagen 1/4 and TGF-β expression[1].
LM9 (24 h) does not affect the viability of mouse primary peritoneal macrophages up to 20 μM[2].
LM9 (10-20 μM; 1 h pretreat) reduces inflammatory responses in mouse primary peritoneal macrophages and RAW264.7 cells exposed to ox-LDL (HY-NP013) by suppressing TLR4-MyD88 complex formation, NF-κB activation, and MAPK phosphorylation[2].
LM9 (10-20 μM; 1 h pretreat) suppresses ox-LDL uptake and foam cell formation in mouse primary peritoneal macrophages, which is associated with reduced CD36 expression[2].
LM9 (10-20 μM; 1 h pretreat) reduces ox-LDL-induced ROS production in mouse primary peritoneal macrophages, and this effect is mediated by MyD88 inhibition[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:H9C2 cells
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Concentration:5; 10 μM
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Incubation Time:1 h pretreat + 12 h with PA
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Result:Significantly reduced the mRNA levels of TNF-α, IL-6, ICAM-1, and BNP.
Markly decreased the protein levels of
collagen 1/4 and TGF-β.
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Cell Line:mouse peritoneal macrophages
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Concentration:5; 10 μM
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Incubation Time:1 h + 24 h with PA
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Result:Reduced PA-induced TNF-α, IL-6, and IL-
1β in mouse peritoneal macrophages.
Exhibited a dose-dependent inhibitory effect on the mRNA levels of proinflammatory gene.
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Cell Line:H9C2 cells
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Concentration:5; 10 μM
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Incubation Time:1 h
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Result:Markly inhibited the degradation and phosphorylation of IκB-α.
Decreased the accumulation of NF-κB p65 in the nucleus.
Markly decreased the protein levels of
collagen 1/4 and TGF-β.
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Cell Line:RAW264.7 cells; mouse primary peritoneal macrophages
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Concentration:10; 20 μM
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Incubation Time:1 h
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Result:Inhibited ox-LDL-induced TLR4-MyD88 complex formation.
Inhibited oxLDL-induced activation of MAPKs.
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Cell Line:RAW264.7 cells
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Concentration:10; 20 μM
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Incubation Time:1 h
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Result:Decreased the accumulation of NF-κB p65 in the nucleus.
LM9 (10 mg/kg; i.g.; every 2 days for 8 weeks) attenuates atherosclerosis in HFD ApoE-/- mice[2].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Male C57BL/6J mice (18-22 g) fed with HFD for 16 weeks[1]
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Dosage:5, 10 mg/kg
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Administration:i.g.; every 2 days; 8 weeks
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Result:Dose-dependently decreased serum CK-MB, CK, triglyceride, total cholesterol, and LDL levels.
Increased HDL levels.
Improved cardiac function indicators (EF%, FS%).
Reduced myocardial TNF-α accumulation, neutrophil infiltration, and mRNA levels of proinflammatory genes (TNF-α, IL-6, ICAM-1).
Decreased collagen deposition and mRNA/protein levels of profibrotic genes (collagen I, collagen IV, TGF-β, BNP).
Inhibited HFD-induced IκB-α degradation.
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Animal Model:Male ApoE-/- mice (8-week-old) fed with HFD for 16 weeks[2]
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Dosage:10 mg/kg
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Administration:i.g.; every 2 days for 8 weeks
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Result:Reduced whole aorta plaque area, aortic root lesion area, α-SMA-positive area, collagen deposition.
Reduced serum TNF-α and IL-6 levels, aortic mRNA levels of IL-1β, TNF-α, IL-6, ICAM, and VCAM, CD68-positive macrophage infiltration.
Reduced CD36 expression (mRNA and protein in aortas), and DHE-positive ROS levels in aortas.
Did not alter body weight or serum lipid levels (TG, TCH, LDL, HDL).
Chemical Information
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No. CAS 2249864-11-5
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Peso molecular 497.57
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Fòrmula C24H27N5O5S
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SMILES
O=C(CCN1CCN(CC1)CC2=CC([N+]([O-])=O)=CC=C2)NC3=NC(C4=CC(OC)=C(O)C=C4)=CS3
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
Referencias
[1]. Zheng XY, et al. Compound LM9, a novel MyD88 inhibitor, efficiently mitigates inflammatory responses and fibrosis in obesity-induced cardiomyopathy. Acta Pharmacol Sin. 2020;41(8):1093-1101. [Content Brief]
[2]. Chen T, et al. A novel MyD88 inhibitor LM9 prevents atherosclerosis by regulating inflammatory responses and oxidative stress in macrophages. Toxicol Appl Pharmacol. 2019;370:44-55. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
LM9 Related Classifications
HY-180336 Related Classifications
Powered by Bioz
- LM9
- 2249864-11-5
- LM 9
- LM-9
- MyD88
- Toll-like Receptor (TLR)
- NF-κB
- Collagen
- TGF-β Receptor
- p38 MAPK
- Reactive Oxygen Species (ROS)
- MyD88 homodimer formation
- macrophages
- atherosclerosis
- ox-LDL
- TLR4/MyD88/NF-κB signaling pathway
- TLR4/MyD88 binding
- obesity-induced cardiomyopathy
- cardiac cells
- high-fat diet-fed mice
- Inhibitor
- inhibitor
- inhibit