Zotarolimus(ABT-578)

Zotarolimus(ABT-578)是一种专用于冠脉药物洗脱支架的抗增殖药物[1].

Zotarolimus(ABT-578)是雷帕霉素的类似物,是一种抗增殖药物.Zotarolimus对免疫亲和素FKBP12具有高亲和性,可抑制T细胞增殖[1].Zotarolimus可抑制FKBP-12结合,IC50值为2.8 nM.在人类冠状动脉细胞中,zotarolimus可抑制平滑肌细胞(SMC)和内皮细胞(EC)增殖,IC50值分别为2.9和2.6 nM[2].在人类血液来源的外周血单核细胞(PBMC)和大鼠脾细胞中,zotarolimus可以浓度依赖的方式抑制Con A诱导的人类和大鼠T细胞增殖,IC50值分别为7.0和1337 nM.在源自人类或大鼠的淋巴细胞中,zotarolimus可以浓度依赖的方式抑制人类和大鼠的混合淋巴细胞反应(MLR),IC50值分别为1.2和1465 nM.并且,zotarolimus可抑制生长因子诱导的人类冠状动脉平滑肌细胞增殖,IC50值为0.8 nM[3].

在杂交幼猪中,zotarolimus洗脱的PC覆盖支架可减少肠腔狭窄百分率\减少内膜面积\减少内膜厚度和增加管腔面积[2].在T细胞介导的大鼠佐剂DTH模型中,zotarolimus可抑制大鼠佐剂DTH响应,ED50值为1.72 mg/kg/天[2].

参考文献：
[1].  Brugaletta S, Burzotta F, Sabaté M. Zotarolimus for the treatment of coronary artery disease: pathophysiology, DES design, clinical evaluation and future perspective. Expert Opin Pharmacother, 2009, 10(6): 1047-1058.
[2].  Garcia-Touchard A, Burke SE, Toner JL, et al. Zotarolimus-eluting stents reduce experimental coronary artery neointimal hyperplasia after 4 weeks. Eur Heart J, 2006, 27(8): 988-993.
[3].  Chen YW, Smith ML, Sheets M, et al. Zotarolimus, a novel sirolimus analogue with potent anti-proliferative activity on coronary smooth muscle cells and reduced potential for systemic immunosuppression. J Cardiovasc Pharmacol, 2007, 49(4): 228-235.