A-770041

一种口服生物可利用的LCK激酶抑制剂(IC50=0.147µM)；对LCK的选择性优于Src、Fyn、Fgr、HCK和Tie2（IC50s分别为9.05、44.1、14.1、1.22和>50µM）；抑制分离的人全血中抗CD3抗体和PMA诱导的IL-2产生（EC50=80nM）以及大鼠中刀豆球蛋白A诱导的IL-2产生；在10mg/kg剂量下，可在异位心脏移植大鼠模型中预防急性排斥反应并提高移植物存活率；抑制CTV-1细胞的生长（IC50=224nM）并使U2OSMR和KHOSR2多药耐药人骨肉瘤细胞对紫杉醇和阿霉素敏感。An orally bioavailable LCK kinase inhibitor (IC50 = 0.147 µM); selective for LCK over Src, Fyn, Fgr, HCK, and Tie2 (IC50s = 9.05, 44.1, 14.1, 1.22, and >50 µM, respectively); inhibits IL-2 production induced by an anti-CD3 antibody and PMA in isolated human whole blood (EC50 = 80 nM) and by concanavalin A in rats; prevents acute rejection and increases graft survival in a rat model of heterotopic heart transplantation at 10 mg/kg; inhibits the growth of CTV-1 cells (IC50 = 224 nM) and sensitizes U2OSMR and KHOSR2 multidrug resistant human osteosarcoma cells to paclitaxel and doxorubicin.分子式C34H39N9O3分子量621.7NC1=C2C(C3=CC(OC)=C(C=C3)NC(C4=CC5=CC=CC=C5N4C)=O)=NN([C@@]6([H])CC[C@@](N7CCN(CC7)C(C)=O)([H])CC6)C2=NC=N1