Inflachromene
(Synonyms: 炎性色素,ICM) 目录号 : GC40924Inflachromene 是HMGB1和HMGB表达的抑制剂。Inflachromene可以抑制HMGB1的释放和NF-κB信号通路，发挥抗炎和神经保护作用。Inflachromene主要用于治疗癫痫。
Cas No.:908568-01-4
Sample solution is provided at 25 µL, 10mM.
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Inflachromene is an inhibitor of HMGB1 and HMGB expression. Inflachromene can inhibit the release of HMGB1 and the NF-κB signaling pathway, exerting anti-inflammatory and neuroprotective effects. Inflachromene is mainly used to treat epilepsy [1-4].
In VSMC cells, Inflachromene (5, 10, 15, and 20μM, 24h) dramatically decreased Ang II–induced VSMC proliferation [5]. In HEK293T cells, Inflachromene (25 and 50μM, 6h) dramatically decreased the endogenous Beclin 1 protein level in a dose- and time-dependent manner whereas the levels of ATG5–ATG12 conjugate, ATG7 and ATG16L1 were not changed [6]. Inflachromene (10μM, 6d) induces senescence rapidly and homogeneously in the popular fetal lung fibroblast (IMR90) cell model, while also constraining SASP production and its paracrine effects [7].
In C57BL/6 mouse, Inflachromene (5 and 10mg/kg, ip, 14d) attenuated the neointimal formation induced by the carotid wire injury in mice [5]. In PTZ-induced seizure model, Inflachromene (3 and 10mg/kg, ip, single injection) alleviates the severity of PTZ-induced seizures in a dose-dependent manner [8]. In sepsis-associated encephalopathy (SAE) mice model, Inflachromene (10mg/kg, ip, 9d) improves cognitive impairment in SAE mice by inhibiting HMGB1-mediated microglial activation, alleviating synaptic damage and neuronal dysfunction [9]. In carbon tetrachloride (CCl4) induced liver fibrosis mouse model, Inflachromene (10mg/kg, ip, 28d) reduces HMGB2 expression and function and protects mice from liver fibrosis [10].
References:
[1]. Lee S, Nam Y, Koo JY, et al. A small molecule binding HMGB1 and HMGB2 inhibits microglia-mediated neuroinflammation. Nature chemical biology. 2014 Dec; 10(12): 1055-1060.
[2]. Teng S, Zhu Z, Wu C, et al. Inflachromene inhibits intimal hyperplasia through the HMGB1/2-regulated TLR4-NF-κB pathway. International Immunopharmacology. 2023 Jun 1; 119: 110198.
[3]. Lee HH, Im SH, Ahn S, et al. A validated UPLC-MS/MS method for pharmacokinetic study of inflachromene, a novel microglia inhibitor. Journal of Pharmaceutical and Biomedical Analysis. 2019 Mar 20; 166: 183-188.
[4]. Zhang S, Chen F, Zhai F, et al. Role of HMGB1/TLR4 and IL-1β/IL-1R1 signaling pathways in epilepsy. Frontiers in neurology. 2022 Jun 28; 13: 904225.
[5]. Teng S, Zhu Z, Wu C, et al. Inflachromene inhibits intimal hyperplasia through the HMGB1/2-regulated TLR4-NF-κB pathway. International Immunopharmacology. 2023 Jun 1; 119: 110198.
[6]. Kim YH, Kwak MS, Shin JM, et al. Inflachromene inhibits autophagy through modulation of Beclin 1 activity. Journal of Cell Science. 2018 Feb 15; 131(4): jcs211201.
[7]. Palikyras S, Sofiadis K, Stavropoulou A, et al. Rapid and synchronous chemical induction of replicative‐like senescence via a small molecule inhibitor. Aging Cell. 2024 Apr; 23(4): e14083.
[8]. Dai SJ, Shao YY, Zheng Y, et al. Inflachromene attenuates seizure severity in mouse epilepsy models via inhibiting HMGB1 translocation. Acta Pharmacologica Sinica. 2023 Sep; 44(9): 1737-1747.
[9]. Yin XY, Tang XH, Wang SX, et al. HMGB1 mediates synaptic loss and cognitive impairment in an animal model of sepsis-associated encephalopathy. Journal of Neuroinflammation. 2023 Mar 11; 20(1): 69.
[10]. Huang Y, Liangpunsakul S, Rudraiah S, et al. HMGB2 is a potential diagnostic marker and therapeutic target for liver fibrosis and cirrhosis. Hepatology Communications. 2023 Nov 1; 7(11): e0299.
Inflachromene 是HMGB1和HMGB表达的抑制剂。Inflachromene可以抑制HMGB1的释放和NF-κB信号通路，发挥抗炎和神经保护作用。Inflachromene主要用于治疗癫痫 [1-4]。
在VSMC细胞中，Inflachromene（5、10、15和20μM，24h）显著抑制血管紧张素II诱导的平滑肌细胞增殖 [5]。在HEK293T细胞中，Inflachromene（25和50μM，6h）以剂量和时间依赖性方式显著降低内源性Beclin 1蛋白水平，而ATG5-ATG12结合物、ATG7和ATG16L1的水平则没有变化 [6]。Inflachromene（10μM，6d）在常用的胎儿肺成纤维细胞（IMR90）模型中快速均匀地诱导细胞衰老，同时抑制SASP的产生及其旁分泌作用 [7]。
在C57BL/6小鼠中，Inflachromene（5和10mg/kg，ip，14d）可减弱小鼠颈动脉导线损伤引起的新生内膜形成 [5]。在PTZ诱发的癫痫模型中，Inflachromene（3和10mg/kg，ip，1次）以剂量依赖性方式减轻戊四氮诱发的癫痫严重程度 [8]。在脓毒症相关脑病（SAE）小鼠模型中，Inflachromene（10mg/kg，ip，9d）通过抑制HMGB1介导的小胶质细胞活化，减轻突触损伤和神经元功能障碍，改善SAE小鼠的认知障碍 [9]。在四氯化碳（CCl4）诱导的肝纤维化小鼠模型中，Inflachromene（10mg/kg，ip，28d）降低HMGB2的表达和功能，保护小鼠免于肝纤维化 [10]。
| Cell experiment [1]: | |
Cell lines | VSMC cells |
Preparation Method | Cell viability was measured using cell counting kit-8 (CCK-8, Dojindo) in order to choose suitable Inflachromene concentrations. For the viability assay, VSMCs were pretreated with Inflachromene (5, 10, 15, and 20μM) for 24h. |
Reaction Conditions | 5, 10, 15, and 20μM; 24h |
Applications | Inflachromene dramatically decreased Ang II–induced VSMC proliferation. |
| Animal experiment [2]: | |
Animal models | PTZ-induced seizure model |
Preparation Method | PTZ induced seizure model was conducted. Stainless steel screws were screwed into the dorsal aspect of the anterior fontanelle, the bilateral sensory cortex and the ventral aspect of the posterior fontanelle, and fixed with dental cement. The anterior and posterior screws were used as cortical EEG recording and grounding, respectively. Mice were treated with 3 and 10mg/kg Inflachromene or vehicle 15 minutes before the injection of PTZ (80mg/kg, ip). |
Dosage form | 3 and 10mg/kg; ip; single injection |
Applications | Inflachromene alleviates the severity of PTZ-induced seizures in a dose-dependent manner. |
References: | |
| Cas No. | 908568-01-4 | SDF | |
| 别名 | 炎性色素,ICM | ||
| 化学名 | 5,12b-dihydro-10-hydroxy-7,7-dimethyl-2-phenyl-1H,7H-[1]benzopyrano[4,3-c][1,2,4]triazolo[1,2-a]pyridazine-1,3(2H)-dione | ||
| Canonical SMILES | OC1=CC(OC(C)(C)C2=CCN(C(N(C3=CC=CC=C3)C4=O)=O)N4C25)=C5C=C1 | ||
| 分子式 | C21H19N3O4 | 分子量 | 377.4 |
| 溶解度 | 2.5mg/mL in ethanol, 30mg/mL in DMSO, or in DMF | 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.6497 mL | 13.2485 mL | 26.4971 mL |
| 5 mM | 0.5299 mL | 2.6497 mL | 5.2994 mL |
| 10 mM | 0.265 mL | 1.3249 mL | 2.6497 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
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1. 首先保证母液是澄清的；
2.
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