TRAF-STOP inhibitor 6877002
目录号 : GC38868
TRAF-STOP inhibitor 6877002是一种抑制CD40-TRAF6相互作用的选择性抑制剂（TRAF-STOPs）。
Cas No.:433249-94-6
Sample solution is provided at 25 µL, 10mM.
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TRAF-STOP inhibitor 6877002 is a selective inhibitor of CD40-TRAF6 interaction (TRAF-STOPs)[1]. Tumor necrosis factor receptor-associated factor 6 (TRAF6) contributes to CD40-mediated activation of NF-κB, stress-activated protein kinases, and possibly other signaling molecules[2]. TRAF-STOP inhibitor 6877002 can be used to treat atherosclerosis[3].
In vitro, TRAF-STOP inhibitor 6877002 (0-20µM) treatment of bone marrow-derived monocytes/macrophages (BMMs) for 5-6 days significantly inhibited CD40L and RANKL-induced differentiation of BMMs into osteoclasts, inhibited NF-κB signaling, and weakened osteoclast bone resorption capacity[4].
In vivo, intraperitoneal injection of TRAF-STOP inhibitor 6877002 (10μM/kg/day) for 6 weeks in apolipoprotein E-deficient (Apoe−/−) mice significantly inhibited atherosclerosis in mice, reduced the size of the necrotic center of plaques, reduced Ly6G+ neutrophils and CD3+ T cells in plaques, and increased collagen and αSMA+ smooth muscle cells[5]. Intraperitoneal injection of TRAF-STOP inhibitor 6877002 (10μM/kg/day) for 6 weeks in diet-induced obese mice significantly reduced the accumulation of CD4+ and CD8+ T cells and macrophages in adipose tissue, reduced hepatic steatosis and improved insulin sensitivity[6].
References:
[1] van Tiel C M, Seijkens T T, Kusters P J, et al. TRAF-STOP-RHDL-Nanoparticles Reduce Atherosclerosis[J]. Arteriosclerosis, Thrombosis, and Vascular Biology, 2017, 37(suppl_1): A224-A224.
[2] Hostager B S. Roles of TRAF6 in CD40 signaling[J]. Immunologic research, 2007, 39: 105-114.
[3] Rouwet E, Lutgens E. 2016 Jeffrey M. Hoeg award lecture: immune checkpoints in atherosclerosis: toward immunotherapy for atheroprotection[J]. Arteriosclerosis, thrombosis, and vascular biology, 2018, 38(8): 1678-1688.
[4] Huang Y, Wu J, Zhan C, et al. TRAF-STOP alleviates osteoclastogenesis in periodontitis[J]. Frontiers in Pharmacology, 2023, 14: 1119847.
[5] Seijkens T T P, van Tiel C M, Kusters P J H, et al. Targeting CD40-induced TRAF6 signaling in macrophages reduces atherosclerosis[J]. Journal of the American College of Cardiology, 2018, 71(5): 527-542.
[6] Chatzigeorgiou A, Seijkens T, Zarzycka B, et al. Blocking CD40-TRAF6 signaling is a therapeutic target in obesity-associated insulin resistance[J]. Proceedings of the National Academy of Sciences, 2014, 111(7): 2686-2691.
TRAF-STOP inhibitor 6877002是一种抑制CD40-TRAF6相互作用的选择性抑制剂（TRAF-STOPs）[1]。肿瘤坏死因子受体相关因子6（TRAF6）有助于CD40介导的NF-κ B、应激活化蛋白激酶和可能的其他信号分子的活化[2]。TRAF-STOP inhibitor 6877002可用于治疗动脉粥样硬化[3]。
在体外，TRAF-STOP inhibitor 6877002（0-20µM）处理骨髓来源的单核细胞/巨噬细胞（BMMs）5-6天，显著抑制了CD40L和RANKL诱导BMMs分化为破骨细胞，并抑制NF-κB信号传导，减弱了破骨细胞骨吸收能力[4]。
在体内，TRAF-STOP inhibitor 6877002（10μM/kg/day）通过腹膜内注射治疗载脂蛋白E缺陷（Apoe−/−）小鼠6周，显著抑制了小鼠动脉粥样硬化，使斑块坏死中心变小，减少了斑块内Ly6G+中性粒细胞和CD3+T细胞，增加了胶原和αSMA+平滑肌细胞[5]。TRAF-STOP inhibitor 6877002（10μM/kg/day）通过腹膜内注射治疗饮食诱导肥胖的小鼠6周，显著减少了脂肪组织中CD4+和CD8+ T细胞以及巨噬细胞的积累，减少了肝脂肪变性并改善胰岛素敏感性[6]。
| Cell experiment [1]: | |
Cell lines | Bone marrow-derived monocytes/macrophages (BMMs) |
Preparation Method | Cells were seeded into 96-well plates at a density of 1×104/well in α-MEM containing 30ng/mL M-CSF and 50ng/ml RANKL without or with CD40L (20ng/ml) and TRAF-STOP inhibitor 6877002 (0–20µM). Cells treated with only M-CSF were used as controls. All cells were incubated in a 37°C incubator under an atmosphere with 5% CO2. Upon observation of multi-nucleated osteoclasts at 5-6 days of culture, TRAP staining was carried out to detect osteoclasts. |
Reaction Conditions | 0-20µM; 5-6 days |
Applications | TRAF-STOP inhibitor 6877002 suppresses CD40L- and RANKL-induced osteoclast differentiation in vitro. |
| Animal experiment [2]: | |
Animal models | Apoe−/− mice |
Preparation Method | Twelve-week-old male Apoe−/− mice were fed a normal chow diet and were intraperitoneal injected for 6 weeks with TRAF-STOP inhibitor 6877002 (n=13), 6860766 (n=12) (10μM/kg/day in 200μl of vehicle), or vehicle control (vehicle: phosphate-buffered saline, 0.05% Tween 80, 5% dimethylsulfoxide) (n=15). Mice were then sacrificed and the arterial tree was perfused. The aortic arch and its main branch points were excised, fixed overnight, and embedded in paraffin. Longitudinal sections of the aortic arch and transversal sections of the aortic root were analyzed for plaque extent and morphology. |
Dosage form | 10μM/kg/day for 6 weeks; i.p. |
Applications | After treatment with TRAF-STOP inhibitor 6877002 or 6860766, atherosclerotic plaques exhibited a stable plaque phenotype. Macrophage number and macrophage proliferation were decreased, and plaques featured smaller necrotic cores. |
References: [1]Huang Y, Wu J, Zhan C, et al. TRAF-STOP alleviates osteoclastogenesis in periodontitis[J]. Frontiers in Pharmacology, 2023, 14: 1119847. [2]Seijkens T T P, van Tiel C M, Kusters P J H, et al. Targeting CD40-induced TRAF6 signaling in macrophages reduces atherosclerosis[J]. Journal of the American College of Cardiology, 2018, 71(5): 527-542. | |
| Cas No. | 433249-94-6 | SDF | |
| Canonical SMILES | O=C(C1=CC=CC=C1)/C=C/NC2=C(C=CC(C)=C2)C | ||
| 分子式 | C17H17NO | 分子量 | 251.32 |
| 溶解度 | DMSO: 125 mg/mL (497.37 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 3.979 mL | 19.895 mL | 39.7899 mL |
| 5 mM | 0.7958 mL | 3.979 mL | 7.958 mL |
| 10 mM | 0.3979 mL | 1.9895 mL | 3.979 mL |
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每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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- Purity: >98.00%
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