| Description | Inflachromene (ICM) is an inhibitor of HMGB1 and HMGB expression with anti-inflammatory activity.Inflachromene reduces seizure severity in a mouse model of epilepsy by inhibiting HMGB1 translocation, inhibits endothelial proliferation through the HMGB1/2-regulated TLR4-NF-κB pathway, and inhibits autophagy by regulating Beclin 1 activity. Inflachromene can be used to study epilepsy. |
| In vitro | 在BV-2微膠細胞中，Inflachromene以劑量依賴的方式高效地阻止LPS誘導的一氧化氮釋放(0.01-100 μM; 24小時)，且無任何毒性[1]。LPS刺激後，Inflachromene(1-10 μM)抑制炎症相關基因如Il6、Il1b、Nos2和Tnf的上調[1]。在5 μM濃度下，Inflachromene減少LPS誘導的促炎細胞因子TNF-α的分泌[1]。在微膠質細胞中，Inflachromene(5 μM; 30分鐘)顯著抑制NF-κB的核內轉移和IκB的降解[1]。LPS誘導的微膠質細胞中ERK、JNK和p38 MAPK的磷酸化被Inflachromene(1-10 μM; 30分鐘)抑制[1]。在神經母細胞瘤與初級神經細胞的共培養中，Inflachromene(10 μM; 30分鐘)通過抑制微膠質細胞介導的神經毒性完全防止了細胞死亡[1]。對於神經元的活性，Inflachromene(1-10 μM; 24小時)沒有顯著影響[1]。 |
| In vivo | 以剂量依赖的方式 (2-10 mg/kg；每日一次，连续四天)，Inflachromene 有效阻断了LPS介导的小胶质细胞激活[1]。在30天的时间里（10 mg/kg；每日一次），Inflachromene 显著减缓了疾病的进展，如EAE临床评分所确定[1]。通过静脉注射（i.v.）以1 mg/kg的剂量给药时，Inflachromene 表现出较长的半衰期（14.1±6.43小时）和中等的稳态体积分布（Vss）（2.02±1.02 L/kg）[2]。口服给药（p.o.）1 mg/kg剂量时，Inflachromene 展现出高口服生物利用度（94%）和最大血浆浓度（Cmax）（0.59±0.16 g/mL）[2]。 |
| Synonyms | ICM |
| molecular weight | 377.39 |
| Molecular formula | C21H19N3O4 |
| CAS | 908568-01-4 |
| Storage | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| Solubility | DMSO: 80 mg/mL (211.98 mM), Sonication is recommended. |
| References | 1. Lee S, et, al. A small molecule binding HMGB1 and HMGB2 inhibits microglia-mediated neuroinflammation. Nat Chem Biol. 2014 Dec; 10(12): 1055-60. 2. Lee HH, et al. A validated UPLC-MS/MS method for pharmacokinetic study of inflachromene, a novel microglia inhibitor. J Pharm Biomed Anal. 2019 Mar 20; 166: 183-188. 3. Cho W, Koo JY, Park Y, Oh K, Lee S, Song JS, Bae MA, Lim D, Lee DS, Park SB. Treatment of Sepsis Pathogenesis with High Mobility Group Box Protein 1-Regulating Anti-inflammatory Agents. J Med Chem. 2017 Jan 12;60(1):170-179. doi: 10.1021/acs.jmedchem.6b00954. Epub 2016 Dec 21. PubMed PMID: 28001381. 4. Block ML. Neuroinflammation: modulating mighty microglia. Nat Chem Biol. 2014 Dec;10(12):988-9. doi: 10.1038/nchembio.1691. PubMed PMID: 25393492. |
| Citations | 1. Jiang J, Shao X, Liu W, et al.The mechano-chemical circuit in fibroblasts and dendritic cells drives basal cell proliferation in psoriasis.Cell Reports.2024, 43(7): 114513. |