Small-molecule activation of the TRAIL receptorDR5 in human cancer cells

Gelin Wang, Xiaoming Wang, Hong Yu, Shuguang Wei, Noelle Williams, Daniel L Holmes,Randal Halfmann, Jacinth Naidoo, Lai Wang, Lin Li, She Chen, Patrick Harran, Xiaoguang Lei& Xiaodong Wang

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) activates apoptosis through the death receptors DR4 and DR5. Because of its superior safety profile and high tumor specificity compared to other TNF family members, recombinant soluble TRAIL and agonistic antibodies against its receptors are actively being developed for clinical cancer therapy. Here, we describe the identification and characterization of the small molecules that directly target DR5 to initiate apoptosis in human cancer cells. The activity was initially discovered through a high-throughput chemical screen for compounds that promote cell death in synergy with a small-molecule mimetic ofSmac, the antagonist for inhibitor of apoptosis protein. Structure-activity relationship studies yielded a more potent analog called bioymifi, which can act as a single agent to induce DR5 clustering and aggregation, leading to apoptosis. Thus, this study identified potential lead compounds for the development of small-molecule TRAIL mimics targeting DR5 for cancer therapy.

• 以上资料由西亚试剂：http://www.xiyashiji.com/ 提供此产品的详细信息如密度,含量,分子式,分子量等均可在西亚官网查询   
• 相关产品如诺卡氏菌液(-)-樟脑神经鞘磷脂,从牛脑所得 杨梅苷愈创奥IAPN-叔丁基苯硫腈氯化物4-溴苯基五氟化硫色胺盐酸盐4-溴噻吩-2-甲醛纤维素粉 7-(二甲基氨基)-4-三氟甲基香豆素邻硝基苯肼盐酸盐3,3'-二氨基联苯胺四盐酸盐水合物美伐他汀丁卡因阿卡明全氟辛基季胺碘化物布西拉明硫酸多粘菌素B益母草浸膏黄苓干膏 L-2,3-二氨基丙酸盐酸盐黄糊精EB替代品(GoldView)等均有销售.欢迎订购