多发性骨髓瘤
化学
细胞凋亡
IC50型
细胞生长
计算生物学
药理学
体外
癌症研究
生物化学
生物
免疫学
作者
Yi Hou,Wenbin Kuang,Wenjian Min,Ziwen Liu,Fang Zhang,Kai Yuan,Xiao Wang,Chengliang Sun,Hao Cheng,Liping Wang,Yibei Xiao,She-Ban Pu,Gui-Zhong Xin,Peng Yang
标识
DOI:10.1021/acs.jmedchem.1c00087
摘要
Icaritin is an active ingredient in Epimedium, which has a variety of pharmacological activities. However, the low activity of Icaritin and the unclear target greatly limit its application. Therefore, based on the structure of Icaritin, we adopted the strategy of replacing toxic groups and introducing active groups to design and synthesize a series of new analogues. The top compound C3 exhibited better antimultiple myeloma activity with an IC50 of 1.09 μM for RPMI 8226 cells, induced RPMI 8226 apoptosis, and blocked the cell cycle in the S phase. Importantly, transcriptome analysis, cellular thermal shift assay, and microscale thermophoresis assay confirmed that DEPTOR was the target of C3. Moreover, we explored its binding mode with C3. Especially, C3 displayed satisfactory inhibition of tumor growth in RPMI 8226 xenografts without obvious side effects. In summary, C3 was discovered as a novel putative inhibitor of DEPTOR for the treatment of multiple myeloma.
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