Fig. 1: Model of the anti-MM effect of YL064.
From: Sinomenine derivative YL064: a novel STAT3 inhibitor with promising anti-myeloma activity
Different from other kinds of cancer cells, the survival and proliferation of MM cells is highly dependent on the bone marrow microenvironment. Bone marrow stromal cells can confer drug resistance to MM cells through direct contact and/or releasing soluble factors such as IL-6. Consequently, STAT3 is activated by tyrosine phosphorylation (Tyr705), followed by homodimerization, nuclear translocation, DNA binding, and subsequent expression of numerous gene products required for tumor cell survival (e.g., Mcl-1), proliferation (e.g., cyclin D1). YL064 is a derivative of sinomenine, a natural compound in clinical use. YL064 directly interacts with STAT3 through its SH2 domains, which in turn inhibits the Tyr705 phosphorylation of STAT3, and ultimately represses the proliferation and viability MM cells in vitro and in vivo. YL064 is a promising novel candidate STAT3 inhibitor for the treatment of MM
