Dual inhibition of mTORC1/2 by DCZ0358 induces cytotoxicity in multiple myeloma and overcomes the protective effect of the bone marrow microenvironment

Interaction of multiple myeloma (MM) cells with the bone marrow (BM) microenvironment promotes the proliferation, survival and chemoresistance of MM. The mTOR pathway plays a key role in these undesirable BM microenvironment-mediated events. We synthesized a novel alkaloid compound, DCZ0358, that effectively inhibits mTOR signaling via dual mTORC1/2 inhibition and exhibits potent anti-MM activity in cultured and primary MM cells, as well as a MM xenograft model but has little effect on normal cells.

Source: Cancer Letters - February 8, 2018 Category: Cancer & Oncology Authors: Lu Gao, Bo Li, Guang Yang, Peng Liu, Xiucai Lan, Shuaikang Chang, Yi Tao, Zhijian Xu, Bingqian Xie, Xi Sun, Yingcong Wang, Liangning Hu, Dandan Yu, Yongsheng Xie, Wenxuan Bu, Xiaosong Wu, Weiliang Zhu, Jumei Shi Tags: Original Articles Source Type: research