BIO 1211 is an α4β1 (VLA-4) integrin inhibitor, which inhibits α4β1 (IC₅₀=4nM) and α4β7 (IC₅₀=2µM)[1-2]. BIO 1211 reduces leukocyte migration and inflammatory cytokine expression by inhibiting the VLA-4/VCAM-1 interaction. BIO 1211 can be used in research related to inflammatory diseases such as multiple sclerosis (experimental autoimmune encephalomyelitis model) and asthma[3-4].
In vitro, BIO 1211 (50µM) was co-cultured with patient-derived B-ALL bone marrow mononuclear cells and two stromal cell populations (adipogenic progenitor cells and early mesenchymal progenitor cells) for 7 days, effectively reducing the viability of leukemic cells in the co-culture system[5]. IMR-32, CHP-134, and Kelly neuroblastoma cell lines were treated with BIO 1211 (1-5µM) for 72 hours. BIO 1211 significantly decreased cell survival and reduced cell attachment; when combined with the anti-GD2 antibody 14G2a (20 µg/ml), BIO 1211 further enhanced cytotoxicity in IMR-32 cells[6].
In vivo, BIO 1211 (1, 3, 10mg/ml; 2min) was administered via aerosol inhalation to treat SD rats sensitized with albumin. BIO 1211 dose-dependently significantly inhibited the increase in lung resistance and the decrease in dynamic lung compliance caused by antigen challenge[7]. BIO 1211 (1, 3, 10mg/kg) was administered via a single intraperitoneal injection to treat SD rats after glucan gel-induced inflammation. BIO 1211 dose-dependently significantly inhibited the aggregation of peritoneal eosinophils[8].
References:
[1] Bolger GT. BIO-1211 (Biogen). IDrugs. 2000 May;3(5):536-40.
[2] Hagmann WK. The discovery and potential of N-sulfonylated dipeptide VLA-4 antagonists. Curr Top Med Chem. 2004;4(14):1461-71.
[3] Dattoli SD, De Marco R, Baiula M,et al. Synthesis and assay of retro-α4β1 integrin-targeting motifs. Eur J Med Chem. 2014 Feb 12;73:225-32.
[4] Drin G, Cottin S, Blanc E, et al. Studies on the internalization mechanism of cationic cell-penetrating peptides. J Biol Chem. 2003 Aug 15;278(33):31192-201.
[5] Ferrao Blanco MN, Kazybay B, Belderbos M, et al. Distinct stromal cell populations define the B-cell acute lymphoblastic leukemia microenvironment. Leukemia. 2025 Nov;39(11):2622-2639.
[6] Horwacik I, Rokita H. Modulation of interactions of neuroblastoma cell lines with extracellular matrix proteins affects their sensitivity to treatment with the anti-GD2 ganglioside antibody 14G2a. Int J Oncol. 2017 May;50(5):1899-1914.
[7] Dong XW, Du XG, Zhang SJ, et al. Inhibitory effects of BIO-1211 on bronchoconstriction and neutrophil adhesion in rats. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2008 Jul;37(4):340-4.
[8] Zhao XY, Chen JQ, Xie QM, et al. Effects of BIO-1211 on eosinophil chemotaxis, recruitment and mediator release. Zhejiang Da Xue Xue Bao Yi Xue Ban. 2003 Aug;32(4):279-82, 291.
BIO 1211是一种α4β1（VLA-4）整合素抑制剂，可分别抑制α4β1（IC50=4nM）和α4β7（IC50=2μM）[1-2]。BIO 1211通过抑制VLA-4/VCAM-1相互作用来减少白细胞迁移和炎症细胞因子表达。BIO 1211可用于多发性硬化症（实验性自身免疫性脑脊髓炎模型）和哮喘等炎症性疾病的相关研究[3-4]。
在体外，BIO 1211（50μM）与B-ALL患者来源的骨髓单核细胞及两种基质细胞群（脂肪源性祖细胞和早期间充质祖细胞）共培养7天，可有效降低共培养体系中白血病细胞的存活率[5]。BIO 1211（1-5μM）处理IMR-32、CHP-134和Kelly神经母细胞瘤细胞系72小时。BIO 1211显著降低了细胞存活率，并减少了细胞附着；当BIO 1211与抗GD2抗体14G2a（20μg/ml）联合使用时，在IMR-32细胞中进一步增强了细胞毒性[6]。
在体内，BIO 1211（1、3、10mg/ml；2min）通过气雾吸入给药，用于处理卵白蛋白致敏的SD大鼠。BIO-1211呈剂量依赖性地显著抑制了抗原攻击引起的肺阻力升高和动态肺顺应性降低[7]。BIO-1211（1、3、10 mg/kg）通过单次腹腔注射给药，用于处理葡聚糖凝胶致炎后的SD大鼠。BIO 1211呈剂量依赖性地显著抑制了腹腔嗜酸粒细胞的聚集[8]。