A 286982是一种有效的白细胞相关功能抗原-1/细胞内黏附分子-1（LFA-1/ICAM-1）相互作用的非肽抑制剂，在LFA-1/ICAM-1结合试验和LFA-1介导的细胞粘附试验中，其IC50值分别为44和35nM。
Cas No.:280749-17-9
Sample solution is provided at 25 µL, 10mM.
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A 286982 is a potent, nonpeptide inhibitors of leukocyte function-associated antigen-1/ intracellular adhesion molecule-1 (LFA-1/ICAM-1) interaction, with IC50 values of 44 and 35nM in LFA-1/ICAM-1 binding assay and LFA-1-mediated cellular adhesion assay, respectively[1]. The interaction of LFA-1 with ICAM-1 is critical for adhesion and recruitment of immune cells to antigen-presenting cells and for cell killing by NK cells[2].
In vitro, treatment with A-286982 at 22–176nM for 49h dose-dependently reduced Interferon-Stimulated Gene 15 (ISG15)-induced IFN-γ secretion in NK-92 cells[2]. Treatment with 88nM A 286982 for 24-48h inhibited C-C motif chemokine ligand 18 (CCL18) secretion in macrophages and blocked ISG15-induced activation of the Proto-oncogene tyrosine-protein kinase Src (SRC) signaling pathway[3]. Treatment with 100nM A 286982 for 12-24h significantly reduced the expression of the cytotoxic marker GZMB and the activation marker CD69 in CD8⁺T cells isolated from peripheral blood mononuclear cells (PBMCs) co-cultured with A549 cells[4].
References:
[1] Liu G, Link JT, Pei Z, et al. Discovery of novel p-arylthio cinnamides as antagonists of leukocyte function-associated antigen-1/intracellular adhesion molecule-1 interaction. 1. Identification of an additional binding pocket based on an anilino diaryl sulfide lead. J Med Chem. 2000;43(21):4025-4040.
[2] Swaim CD, Scott AF, Canadeo LA, Huibregtse JM. Extracellular ISG15 Signals Cytokine Secretion through the LFA-1 Integrin Receptor. Mol Cell. 2017;68(3):581-590.e5.
[3] Chen RH, Xiao ZW, Yan XQ, et al. Tumor Cell-Secreted ISG15 Promotes Tumor Cell Migration and Immune Suppression by Inducing the Macrophage M2-Like Phenotype. Front Immunol. 2020;11:594775.
[4] Wang CL, Ho AS, Chang CC, et al. Radiotherapy enhances CXCR3highCD8+ T cell activation through inducing IFNγ-mediated CXCL10 and ICAM-1 expression in lung cancer cells. Cancer Immunol Immunother. 2023;72(6):1865-1880.
A 286982是一种有效的白细胞相关功能抗原-1/细胞内黏附分子-1（LFA-1/ICAM-1）相互作用的非肽抑制剂，在LFA-1/ICAM-1结合试验和LFA-1介导的细胞粘附试验中，其IC50值分别为44和35nM[1]。LFA-1与ICAM-1的相互作用对于免疫细胞向抗原呈递细胞的黏附和募集以及NK细胞的细胞杀伤至关重要[2]。
体外实验中，以22-176nM的A 286982处理49h，可剂量依赖性降低干扰素刺激基因5（ISG15）刺激的NK-92细胞分泌IFN-γ的能力[2]。以88nM A 286982处理24-48h，可抑制巨噬细胞分泌CC趋化因子配体18（CCL18），并阻断ISG15诱导的Src原癌基因酪氨酸蛋白激酶（SRC）信号通路的激活[3]。以100nM A 286982处理12-24h，可显著降低与A549细胞共培养的外周血单核细胞（PBMC）分离的CD8⁺T细胞中细胞毒性标志物GZMB和活化标志物CD69的表达[4]。
| Cell experiment [1]: | |
Cell lines | NK-92 |
Preparation Method | MHM24 and TS1/22 antibodies, a small molecule inhibitor of LFA-1 (A-286982), or an antibody against the transferrin receptor (G1/221/12) was pre-incubated with NK-92 cells for 1h prior to the addition of IL-12 and ISG15 for 48h, followed by an IFN-g ELISA of the cell culture supernatants. |
Reaction Conditions | 22, 44, 88 and 176nM; 49h |
Applications | Increasing amounts of either of the MHM24, TS1/22 antibodies or A-286982 reduced the ability of ISG15 to stimulate IFN-g secretion from NK-92 cells, while a control antibody against the transferrin receptor did not. |
References: | |
| Cas No. | 280749-17-9 | SDF | |
| 化学名 | (E)-1-(4-acetylpiperazin-1-yl)-3-[3-nitro-4-(2-propan-2-ylphenyl)sulfanylphenyl]prop-2-en-1-one | ||
| Canonical SMILES | CC(C)C1=CC=CC=C1SC2=C(C=C(C=C2)C=CC(=O)N3CCN(CC3)C(=O)C)[N+](=O)[O-] | ||
| 分子式 | C24H27N3O4S | 分子量 | 453.55 |
| 溶解度 | 30mg/mL in DMSO, or in DMF | 储存条件 | Store at RT |
| 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。 | ||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.2048 mL | 11.0241 mL | 22.0483 mL |
| 5 mM | 441 μL | 2.2048 mL | 4.4097 mL |
| 10 mM | 220.5 μL | 1.1024 mL | 2.2048 mL |
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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 | ||||||||||
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2.
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Quality Control & SDS
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- Purity: >98.00% Appearance: A solid
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