Icaritin is an active ingredient in , 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 exhibited better antimultiple myeloma activity with an IC 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 . Moreover, we explored its binding mode with . Especially, displayed satisfactory inhibition of tumor growth in RPMI 8226 xenografts without obvious side effects. In summary, was discovered as a novel putative inhibitor of DEPTOR for the treatment of multiple myeloma.
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