GSK2982772

RIPK1抑制剂（人类和小鼠酶的IC50分别为16和2,500nM）；在10µM浓度下，对RIPK1的选择性比339种激酶高10,000倍以上；可抑制由TNF-α和caspase抑制剂QVD-OPh联合诱导的U937人单核细胞和L929鼠纤维肉瘤细胞坏死性细胞死亡（IC50分别为6.3和1,300nM）；在3-300nM浓度下降低溃疡性结肠炎患者肠粘膜组织中的IL-1β和IL-6水平；在3、10和50mg/kg浓度下，可提高TNF-α诱发的致死性休克小鼠模型的存活率。A RIPK1 inhibitor (IC50s = 16 and 2,500 nM for the human and mouse enzymes, respectively); >10,000-fold selective for RIPK1 over a panel of 339 kinases at 10 µM; inhibits necrotic cell death induced by a combination of TNF-α and the caspase inhibitor QVD-OPh in U937 human monocytic and L929 murine fibrosarcoma cells (IC50s = 6.3 and 1,300 nM, respectively); decreases IL-1β and IL-6 levels in intestinal mucosa tissue isolated from patients with ulcerative colitis at 3-300 nM; increases survival in a mouse model of TNF-α-induced lethal shock at 3, 10, and 50 mg/kg.