Delanzomib

糜蛋白酶样蛋白酶体活性抑制剂(IC50=3.8nM)；体外预处理浓度为20nM可抑制IκBα降解、NF-κB活化和NF-κB调节基因的表达，包括IκBα、XIAP、TNF-α、IL-1β、ICAM1和VEGF；诱导多发性骨髓瘤细胞系凋亡并抑制一组人类血液和实体肿瘤细胞系的增殖(IC50s=5.6-34.2nM)；每天两次以1.5-4mg/kg的剂量静脉注射时，可减轻RPMI8226人类多发性骨髓瘤小鼠异种移植模型中的肿瘤重量，以13mg/kg的慢性口服剂量可导致肿瘤完全消退；对小鼠脂肪狼疮性肾炎模型有效。An inhibitor of chymotrypsin-like proteasome activity (IC50 = 3.8 nM); pre-treatment in vitro with a concentration of 20 nM inhibits IκBα degradation, NF-κB activation, and the expression of NF-κB-regulated genes, including IκBα, XIAP, TNF-α, IL-1β, ICAM1, and VEGF; induces apoptosis in multiple myeloma cell lines and inhibits proliferation in a panel of human hematologic and solid tumor cell lines (IC50s = 5.6-34.2 nM); reduces tumor weight in an RPMI 8226 human multiple myeloma mouse xenograft model when administered intravenously at doses ranging from 1.5-4 mg/kg twice daily and leads to complete tumor regression at a chronic oral dose of 13 mg/kg; efficacious in a mouse model of fata lupus nephritis.