ZLDI-8

ZLDI-8 is a Notch activating/cleaving enzyme ADAM-17 inhibitor and inhibits the cleavage of Notch protein. ZLDI-8 decreases the expression of pro-survival/anti-apoptosis and epithelial-mesenchymal transition (EMT) related proteins. ZLDI-8 is also a competitive and irreversible tyrosine phosphatase (Lyp) inhibitor with an IC₅₀ of 31.6 μM and a K_i of 26.22 μM. ZLDI-8 inhibits the growth of MHCC97-H cells with an IC₅₀ of 5.32?μM^[1][2]. IC50 & Target: ADAM-17^[1]
IC50: 31.6 μM (Tyrosine phosphatase)^[1]
Ki: 26.22 μM (Tyrosine phosphatase)^[1] In Vitro: ZLDI-8 (0.03-30 μM; 6-72 hours; MHCC97-H cells) treatment reduces cell viability in a time- and dose-dependent manner^[1].
ZLDI-8 (1-10 μM; 6-72 hours; MHCC97-H cells) significantly decreases the level of NICD and the accumulation of NICD in the nucleus. ZLDI-8 could also reduce the expression of pro-survival/anti-apoptosis regulators, Survivin and cIAP1/2. And also increases the expression of epithelial marker E-Cadherin and reduced mesenchymal markers N-Cadherin and Vimentin^[1].
ZLDI-8 enhances chemotherapy effects on tumor cell proliferation blockage, induction of apoptosis and cell-cycle arrest by inhibiting Notch pathway and blocking chemical resistance^[1]. In Vivo: ZLDI-8 (0.2-2 mg/kg; intraperitoneal injection; every two days; for 20 days; nude mice) treatment enhances the effect of Sorafenib on inhibiting tumor growth in nude HCC-bearing mice model^[1].