ZLDI-8

SKU: orb1219284

Description

ZLDI-8 is an inhibitor of Notch activating/cleaving enzyme ADAM-17 and inhibits the cleavage of Notch protein.ZLDI-8; it inhibited the cleavage of NOTCH protein, consequently decreased the expression of pro-survival/anti-apoptosis and EMT related proteins. ZLDI-8 treatment enhanced the susceptibility of HCC cells to a small molecular kinase inhibitor Sorafenib, and chemotherapy agents Etoposide and Paclitaxel. ZLDI-8 treatment enhanced the effect of Sorafenib on inhibiting tumor growth in nude HCC-bearing mice model. In nude HCC-bearing mice model, 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.

Key Properties

• CAS Number: 667880-38-8
• MW: 433.52
• Purity: >98% (HPLC)
• Formula: C₂₄H₂₃N₃O₃S
• SMILES: O=C(/C(C(N1)=O)=C/C2=C(C)N(CCOC3=CC=C(C)C=C3C)C4=C2C=CC=C4)NC1=S
• Target: ADAM-17
• Solubility: DMSO:62.5 mg/mL (144.17 mM; Need ultrasonic)

Bioactivity

• 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. Animal model: Nude mice with MHCC-97H cells. 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.
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• 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. 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. 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. Cell Viability Assay 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. 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
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Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

ADAM-17