LJ-2698
LJ-2698 (FM101) is an orally active adenosine A3 receptor (Adenosine A3 Receptor) antagonist. LJ-2698 blocks adenosine A3 receptor-dependent pro-inflammatory JNK, ERK, and NF-κB signaling pathways. LJ-2698 prevents alveolar cavity enlargement, restores pulmonary function, and inhibits matrix metalloproteinase activity and pulmonary cell apoptosis (apoptosis) in mice. LJ-2698 induces mitochondrial dysfunction, necroptosis, and intrinsic apoptosis. LJ-2698 ameliorates renal injury in mice with diabetic nephropathy, and alleviates diet-induced hepatic inflammation and fibrosis. LJ-2698 can be used in the research of emphysema, diabetic nephropathy, and metabolic dysfunction-associated steatotic liver disease.
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研究用途以外に使用した場合、当社は一切の責任を負いかねます。
- CAS 番号: 945457-84-1
- 分子式: C16H15Cl2N5O2S
- 分子量:412.29
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保管条件:
Please store the product under the recommended conditions in the Certificate of Analysis.
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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生物活性
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化学情報
- 純度とドキュメンテーション
- 参考文献
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Help & FAQs
生物活性
製品説明
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CHO | Inhibition |
38 %
Compound: 9b
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Displacement of [3H]CCPA from human adenosine A1 receptor in CHO cells at 10 uM
Displacement of [3H]CCPA from human adenosine A1 receptor in CHO cells at 10 uM
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[PMID: 17555308] |
| HEK293 | Inhibition |
18 %
Compound: 9b
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Displacement of [3H]CGS21680 from human adenosine A2A receptor expressed in HEK293 cells at 10 uM
Displacement of [3H]CGS21680 from human adenosine A2A receptor expressed in HEK293 cells at 10 uM
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[PMID: 17555308] |
体外実験
LJ-2698 (0.1 μM, 72 h) restores the expression of anti-inflammatory cytokines (Il4, Il10) and M2 macrophage markers (Arg1, Mrc1) in LPS (HY-D1056)-stimulated RAW 264.7 murine macrophages[1].
LJ-2698 (1 μM) potently and selectively inhibits A3AR with an inhibition rate of 88%[3].
LJ-2698 (2-4 μM; 6 h) induces β-arrestin2-mediated lysosomal degradation of A3AR in LPS-stimulated ImKC, and inhibits A3AR-dependent pro-inflammatory signaling pathways, including JNK, ERK and NF-κB[3].
LJ-2698 (2-4 μM; 6-24 h) exerts anti-inflammatory effects in LPS-stimulated primary mouse Kupffer cells and THP-1 human macrophage-like cells by downregulating the expression of pro-inflammatory cytokine genes and the secretion of TNF-α[3].
LJ-2698 (4 μM) induces mitochondrial dysfunction in primary mouse Kupffer cells, HeLa cells, and LPS-stimulated ImKC, including inhibited respiration, reduced ATP production, increased number of damaged mitochondria, and elevated mitochondrial superoxide levels, and its anti-inflammatory effect depends on mitochondrial integrity[3].
LJ-2698 (4 μM; 12 h) activates the p53/AKT1/GSK3β/β-catenin signaling cascade to trigger necroptosis as the dominant cell death pathway, induce mild endogenous apoptosis, and inhibit pyroptosis and exogenous apoptosis in LPS-stimulated ImKC[3].
LJ-2698 (4 μM; 24 h) selectively induces cytotoxicity in LPS-stimulated ImKC and PA-treated hepatocytes, but exerts no such effect in unstimulated ImKC, HSC, or BSA-treated hepatocytes[3].
LJ-2698 (4 μM; 12 h) selectively targets proinflammatory monocyte-derived Kupffer cells (MoKCs) by downregulating proinflammatory gene expression, upregulating cell death-related gene expression and inducing cytotoxicity, while exerting no effect on embryo-derived Kupffer cells (EmKCs)[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:RAW 264.7 (murine macrophage)
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Concentration:0.1 μM
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Incubation Time:48 h (pretreatment); 24 h (co-incubation with LPS)
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Result:Significantly ameliorated LPS-mediated downregulation of Il4 and Il10 anti-inflammatory cytokine mRNA expression.
Significantly restored LPS-mediated downregulation of Arg1 and Mrc1 M2 macrophage marker mRNA expression.
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Cell Line:immortalized mouse Kupffer cells (ImKCs)
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Concentration:2 μM, 4 μM, 4 μM (with wortmannin)
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Incubation Time:6 h (2 μM, 4 μM); treatment duration not specified (4 μM with wortmannin)
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Result:Reduced A3AR and β-arrestin2 protein levels significantly in LPS-stimulated ImKCs.
Left β-arrestin1 levels unchanged.
Rescued A3AR and β-arrestin2 protein levels when co-treated with wortmannin.
Showed a strong positive correlation between A3AR and β-arrestin2 protein expression.
Reduced levels of phosphorylated JNK, ERK, and IκB-α significantly in LPS-stimulated ImKCs.
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Cell Line:immortalized mouse Kupffer cells (ImKCs)
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Concentration:4 μM
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Incubation Time:12 h
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Result:Activated the p53/AKT1/GSK3β/β-catenin signaling cascade in LPS-stimulated ImKCs.
Elevated levels of phosphorylated RIP3 and MLKL (key necroptosis markers) markedly.
Increased cleaved caspase-3 (intrinsic apoptosis marker).
Decreased cleaved caspase-8, caspase-7, caspase-1, and GSDMD (pyroptosis and extrinsic apoptosis markers).
体内実験
Oral administration of LJ-2698 (1.5-10 mg/kg; p.o.; daily; 12 weeks) for 12 weeks improves diabetic nephropathy in db/db mice in a dose-dependent manner, and the 10 mg/kg dose exhibits the most stable and comprehensive renoprotective effects across all tested indicators[2].
FM101 (30-60 mg/kg; p.o.; daily; 6 weeks), administered daily at doses of 30 or 60 mg/kg for 6 weeks, improves FFD-induced MASLD in C57BL/6 N mice by alleviating hepatic inflammation, fibrosis, and the number of proinflammatory monocyte-derived Kupffer cells; the 60 mg/kg dose also reduces liver weight and liver-to-body weight ratio[3].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:FVB mice (8-week-old)[1]
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Dosage:50 μg/kg
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Administration:p.o.; 6 times per week; 5 weeks
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Result:Restored lung compliance and tissue elasticity to levels closer to control mice.
Markedly suppressed PPE-induced airspace enlargement and reduced the elevated PPE-induced mean linear intercept (MLI).
Suppressed PPE-mediated increases in matrix metalloproteinase gelatinase activity in lung tissue.
Significantly reduced the number of TUNEL-positive apoptotic cells in the lungs compared to PPE-only treated mice.
Restored PPE-induced downregulation of anti-inflammatory cytokine (Il4, Il10) and M2 macrophage marker (Arg1, Mrc1/CD206) mRNA expression in lung tissue.
Increased the number of CD206-positive M2 macrophages per field in lung tissue.
Caused no significant changes in body weight compared to control or PPE-only groups, indicating minimal toxicity.
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Animal Model:C57BLKS/J-db/db (male, 8 weeks old)[2]
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Dosage:1.5 mg/kg; 5 mg/kg; 10 mg/kg
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Administration:p.o.; daily; 12 weeks
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Result:Significantly reduced elevated glomerular volume and fractional mesangial area across all three doses, with no significant differences between doses.
Significantly reduced increased urinary albumin excretion at 5 and 10 mg/kg doses; did not produce a significant reduction at 1.5 mg/kg dose.
Significantly prevented reduced nephrin mRNA levels and increased NGAL mRNA levels at 10 mg/kg dose.
Significantly inhibited increased TGF-β mRNA levels at 10 mg/kg dose; did not produce a significant reduction at 1.5 and 5 mg/kg doses.
Significantly reduced increased collagen IV and fibronectin mRNA levels at 5 and 10 mg/kg doses.
Significantly reduced elevated MCP-1 mRNA levels at 5 and 10 mg/kg doses; significantly inhibited increased ICAM-1 mRNA levels at 10 mg/kg dose, while 1.5 and 5 mg/kg doses did not.
Significantly decreased increased urinary LPO levels at 5 and 10 mg/kg doses.
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Animal Model:C57BL/6N (age 8 weeks at study start; fed high-fat, high-cholesterol fast-food diet with fructose and glucose in drinking water for 24 weeks)[3]
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Dosage:30 mg/kg; 60 mg/kg
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Administration:p.o.; daily; 6 weeks
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Result:Significantly reduced body weight, serum alanine aminotransferase (ALT) levels, serum cholesterol levels, NAFLD Activity Score, hepatic collagen deposition (Sirius Red-positive area), mRNA expression of pro-inflammatory genes (Ccl2, Ccl3, Cxcl2), mRNA expression of profibrogenic genes (Col1a1, Col1a4, Lox, Timp1), hepatic levels of phosphorylated AKT, JNK, and P65, and the percentage of CLEC4F-positive Kupffer cells at 30 mg/kg dose compared to FFD-fed vehicle controls.
Significantly reduced body weight, liver weight, liver-to-body weight ratio, serum ALT levels, serum cholesterol levels, NAFLD Activity Score, hepatic collagen deposition (Sirius Red-positive area), mRNA expression of pro-inflammatory genes (Ccl2, Ccl3, Cxcl2), mRNA expression of profibrogenic genes (Col1a1, Col1a4, Lox, Timp1), hepatic levels of phosphorylated AKT, JNK, and P65, and the percentage of CLEC4F-positive Kupffer cells at 60 mg/kg dose compared to FFD-fed vehicle controls.
化学情報
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CAS 番号 945457-84-1
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分子量 412.29
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分子式 C16H15Cl2N5O2S
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SMILES
N(CC1=CC(Cl)=CC=C1)C2=C3C(N(C=N3)[C@H]4[C@H](O)[C@H](O)CS4)=NC(Cl)=N2
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別名
FM101
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輸送条件
Room temperature in continental US; may vary elsewhere.
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保管条件
Please store the product under the recommended conditions in the Certificate of Analysis.
純度とドキュメンテーション
参考文献
[1]. Boo HJ, et al. LJ-2698, an Adenosine A3 Receptor Antagonist, Alleviates Elastase-Induced Pulmonary Emphysema in Mice. Biomol Ther (Seoul). 2020;28(3):250-258. [Content Brief]
[2]. Dorotea D, et al. Orally active, species-independent novel A3 adenosine receptor antagonist protects against kidney injury in db/db mice. Exp Mol Med. 2018 Apr 20;50(4):1-14. [Content Brief]
[3]. Park JS, et al.. A3AR antagonism mitigates metabolic dysfunction-associated steatotic liver disease by exploiting monocyte-derived Kupffer cell necroptosis and inflammation resolution. Metabolism: clinical and experimental. 2025 Mar;164:156114. [Content Brief]
Calculators
濃度 (開始) × 体積 (開始) = 濃度 (終了) × 体積 (終了)
LJ-2698 関連分類
HY-153149 関連分類
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