CA-074 Me (CA-074 methyl ester) is a specific inhibitor of Cathepsin B(CB)[1-5].
CA-074 Me pretreated 2h with a range of doses can protect lethal toxin-sensitive macrophages from cell death and prevents the activation of caspase-1[1]. CA-074 Me(5μM and 50μM,48h) also inhibits RANK-ligand induced osteoclastogenesis in bone marrow-derived monocyte cells[2].CA-074 Me (20μM, 24h), also partially attenuated free fatty acid induced apoptosis[3].
CA-074 Me (4mg/kg/day, 7day, i.m.) reduced CB expression,decreased inflammation score and attenuated apoptosis in muscle tissues of the guinea-pig model of CVB1-induced polymyositis[4]. CA-074 Me (1μg, 1h, intracerebroventricularly) pretreatment inhibits lysosomal membrane rupture induced by 20-min global cerebral ischemia/reperfusion injury in Sprague-Dawley rats[5].
References:
[1] Newman Z L, Leppla S H, Moayeri M. CA-074 Me protection against anthrax lethal toxin[J]. Infection and immunity, 2009, 77(10): 4327-4336.
[2] Patel N, Nizami S, Song L, et al. CA-074 Me compound inhibits osteoclastogenesis via suppression of the NFATc1 and c‐FOS signaling pathways[J]. Journal of Orthopaedic Research, 2015, 33(10): 1474-1486..
[3] Wu X, Zhang L, Gurley E, et al. Prevention of free fatty acid-induced hepatic lipotoxicity by 18β-glycyrrhetinic acid through lysosomal and mitochondrial pathways[J]. Hepatology, 2008, 47(6): 1905-1915.
[4] Feng Y, Ni L, Wang Q. Administration of cathepsin B inhibitor CA-074 Me reduces inflammation and apoptosis in polymyositis[J]. Journal of dermatological science, 2013, 72(2): 158-167.
[5] Xu Y, Wang J, Song X, et al. Protective mechanisms of CA074-me (other than cathepsin-B inhibition) against programmed necrosis induced by global cerebral ischemia/reperfusion injury in rats[J]. Brain Research Bulletin, 2016, 120: 97-105.
CA-074 Me（CA-074甲酯）是组织蛋白酶B（CB）的特异性抑制剂[1-5]。
CA-074 Me预处理2小时，在一定剂量范围内CA-074 Me可保护致命毒素敏感巨噬细胞免于细胞死亡，并阻止caspase-1的激活[1]。CA-074 Me（5μM和50μM，48小时）还可抑制骨髓来源的单核细胞中RANK配体诱导的破骨细胞生成[2]。CA-074 Me（20μM, 24小时）也能部分减弱游离脂肪酸诱导的细胞凋亡[3]。
CA-074 Me（4mg/kg/天，7天，肌肉注射）降低了豚鼠CVB1诱发的多发性肌炎模型中肌肉组织中的CB表达，降低炎症评分，并减轻细胞凋亡[4]。CA-074 Me（1μg，1小时，侧脑室注射）预处理可抑制Sprague-Dawley大鼠20分钟全脑缺血/再灌注损伤引起的溶酶体膜破裂[5]。