ZLDI-8

ZLDI-8 (CAS No.: 667880-38-8) is a small-molecule inhibitor of the Notch-activating and cleaving enzyme ADAM-17, widely utilized in studies of Notch signaling and tumor cell biology. By blocking ADAM-17–mediated proteolytic cleavage of Notch receptors, ZLDI-8 suppresses downstream signaling events and reduces the expression of pro-survival, anti-apoptotic, and epithelial–mesenchymal transition (EMT)-associated proteins, thereby providing a useful tool for dissecting pathways involved in cell survival, migration, and phenotypic plasticity. In addition to its activity against ADAM-17, ZLDI-8 has been reported to function as a competitive and irreversible inhibitor of lymphoid tyrosine phosphatase (Lyp), indicating potential utility in studies of phosphatase-regulated signaling networks. In vitro, ZLDI-8 inhibits the proliferation of MHCC97-H hepatocellular carcinoma cells with activity in the low micromolar range, and exhibits concentration-dependent cytotoxicity at higher micromolar levels while showing minimal effects at lower concentrations. Experimental evidence further demonstrates that ZLDI-8 can enhance cellular sensitivity to kinase inhibitors and cytotoxic agents in cancer cell models, as well as augment tumor growth suppression in xenograft systems when used in combination paradigms. Accordingly, ZLDI-8 is broadly applied in mechanistic studies of Notch signaling, EMT regulation, and combination strategy screening, with experimental concentrations or dosing regimens tailored to specific cellular or in vivo research objectives.