A 205804 is a potent and selective lead inhibitor of E-selectin and ICAM-1 expression (E-selectin: IC50 = 20nM; ICAM-1: IC50 = 25nM) [1]. A 205804 exerts anti-inflammatory effects by inhibiting the NF-κB signaling pathway and reducing the expression of E-selectin and ICAM-1 [1-2]. A 205804 is often used in the study of chronic inflammatory diseases [3].
In H9 cells, as the dose of A 205804 (1, 3, 5, and 10μM; 24h) increased, the expression level of ICAM-1 protein decreased [4]. In MDA-MB-231 cells, A 205804 (1 and 10μM; 12h) treatment reduced the expression of ICAM-1, whereas the expression of FAK, Src, paxillin, and heparanase was not affected [5].
In pancreatitis mice model, Lung tissue pathological damage, neutrophil infiltration, and pulmonary edema were significantly alleviated in mice after A 205804 (10mg/kg; po; 2 weeks) treatment [6]. In C56BL/6 mice, A 205804 (10mg/kg; po; 2 weeks) treatment of mice can effectively reduce the expression of E-selectin in endothelial vascular microenvironment cells [7]. In H1975 cell xenograft mouse model, A 205804 (10mg/kg; po; 2 weeks) blocks ICAM-1 and p-Cortactin expression by inhibiting the activity of Erβ [8].
References:
[1]. Stewart AO, Bhatia PA, McCarty CM, et al. Discovery of inhibitors of cell adhesion molecule expression in human endothelial cells. 1. Selective inhibition of ICAM-1 and E-selectin expression. Journal of medicinal chemistry. 2001 Mar 15; 44(6): 988-1002.
[2]. Yu R, Hou C, Peng Y, et al. The mechanism underlying ICAM-1 and E-selectin-mediated hypertriglyceridemic pancreatitis-associated lung injury. Molecular Immunology. 2022 Dec 1; 152: 55-66.
[3]. Liu F, Mao Y, Yan J, et al. Bionic microbubble neutrophil composite for inflammation-responsive atherosclerotic vulnerable plaque pluripotent intervention. Research. 2022 Jun 2.
[4]. Wu H, Tang X, Wang Y, et al. Dextran sulfate prevents excess aggregation of human pluripotent stem cells in 3D culture by inhibiting ICAM1 expression coupled with down-regulating E-cadherin through activating the Wnt signaling pathway. Stem Cell Research & Therapy. 2022 May 26; 13(1): 218.
[5]. Wei RR, Sun DN, Yang H, et al. CTC clusters induced by heparanase enhance breast cancer metastasis. Acta Pharmacologica Sinica. 2018 Aug;39(8):1326-1337.
[6]. Yu R, Hou C, Peng Y, Zhu X, Shi C, Huang D, Miao Y, Li Q. The mechanism underlying ICAM-1 and E-selectin-mediated hypertriglyceridemic pancreatitis-associated lung injury. Molecular Immunology. 2022 Dec 1; 152: 55-66.
[7]. Morita K, Tokushige C, Maeda S, et al. RUNX transcription factors potentially control E-selectin expression in the bone marrow vascular niche in mice. Blood Advances. 2018 Mar 13;2(5):509-515.
[8]. Wang Y, Qiu W, Chen J, et al. ERβ promoted invadopodia formation‐mediated non‐small cell lung cancer metastasis via the ICAM1/p‐Src/p‐Cortactin signaling pathway. International journal of cancer. 2023 Sep 15; 153(6): 1287-1299.
A 205804是一种强效、选择性的E-选择素和ICAM-1表达抑制剂（E-选择素：IC50 = 20nM；ICAM-1：IC50 = 25nM） [1]。A 205804通过抑制NF-κB信号通路并降低E-选择素和ICAM-1的表达发挥抗炎作用 [1-2]。A 205804常用于慢性炎症疾病的研究 [3]。
在H9细胞中，随着A 205804剂量（1、3、5 和10μM；24h）的增加，ICAM-1蛋白的表达水平降低 [4]。在MDA-MB-231细胞中，A 205804（1和10μM；12h）处理可降低ICAM-1的表达，而FAK、Src、桩蛋白和肝素酶的表达不受影响 [5]。
在胰腺炎小鼠模型中，A 205804（10mg/kg；po；2周）处理后，小鼠肺组织病理损伤、中性粒细胞浸润及肺水肿均明显减轻 [6]。在C56BL/6小鼠中，A 205804（10mg/kg；po；2周）处理小鼠可有效降低内皮血管微环境细胞中E-选择素的表达 [7]。在H1975细胞异种移植小鼠模型中，A 205804（10mg/kg；po；2周）通过抑制Erβ的活性来阻断ICAM-1和p-Cortactin的表达 [8]。