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]. Animal Model: Nude mice with MHCC-97H cells[1] Dosage: 2 mg/kg, 1 mg/kg, 500 μg/kg, or 200 μg/kg Administration: Intraperitoneal injection; every two days; for 20 days Result: Inhibited tumor growth in nude HCC-bearing mice model.
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]. Cell Viability Assay[1] Cell Line: MHCC97-H cells Concentration: 0.03 μM, 0.1 μM, 0.3 μM, 1 μM, 3 μM, 10 μM, 30 μM Incubation Time: 6 hours, 12 hours, 24 hours, 48 hours, 72 hours Result: Emerged cytotoxic effect on MHCC97-H cells in a time- and dose-dependent manner. Western Blot Analysis[1] Cell Line: MHCC97-H cells Concentration: 1 μM, 3 μM, 10 μM Incubation Time: 6 hours, 12 hours, 24 hours, 48 hours, 72 hours Result: Significantly decreased the level of NICD and the accumulation of NICD in the nucleus. Also reduced the expression of pro-survival/anti-apoptosis regulators, Survivin and cIAP1/2
Kinase Assay
Cell Assay
Animal Administration
References
[1]. Zhang Y, et al. Novel ADAM-17 inhibitor ZLDI-8 enhances the in vitro and in vivo chemotherapeutic effects of Sorafenib on hepatocellular carcinoma cells. Cell Death Dis. 2018 Jul 3;9(7):743.
[2]. Hou X, et al. Fast identification of novel lymphoid tyrosine phosphatase inhibitors using target-ligand interaction-based virtual screening. J Med Chem. 2014 Nov 26;57(22):9309-22.
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