HBS-101

HBS-101 is a first-in-class small-molecule inhibitor of Midkine (MDK), a heparin-binding growth factor and cytokine that is frequently overexpressed in aggressive malignancies, including triple-negative breast cancer (TNBC). MDK signaling is known to promote tumor progression, epithelial-mesenchymal transition, stemness, and an immunosuppressive tumor microenvironment. HBS-101 functions by disrupting MDK-mediated oncogenic signaling pathways, specifically inhibiting STAT3 signaling, which leads to reduced tumor cell viability and increased apoptosis. Preclinical studies have demonstrated that HBS-101 exhibits synergistic anti-tumor activity when combined with standard chemotherapies (such as doxorubicin and paclitaxel) and immune checkpoint inhibitors (such as PD-L1 inhibitors). This combination therapy enhances the infiltration and activity of CD8+ T cells and macrophages while suppressing immunosuppressive signals, thereby overcoming resistance and improving therapeutic outcomes in TNBC models.