Zosuquidar trihydrochloride

SKU: orb1225979

Description

A potent P-glycoprotein (P-gp) inhibitor with Ki of 60 nM; fully restores sensitivity to vinblastine, doxorubicin, etoposide, and Taxol in CEM/VLB100 cells at 0.1 uM; enhances the antitumor activity of Taxol in a MDR human non-small cell lung carcinoma nude mouse xenograft model.Blood Cancer Phase 3 Discontinued(In Vitro):Zosuquidar (0.3 μM; 48 h) enhances the cytotoxicity of DNR (substrates for P-glycoproteins) in P-glycoproteins active cell lines.Zosuquidar (5-16 μM; 72 h) treatment alone shows high cytotoxic concentration to drug-sensitive and MDR cell lines.(In Vivo):Zosuquidar (intraperitoneal injection; 30, 10, 3, or 1 mg/kg; once daily; 5 d) treatment shows a significant increase in life span.Zosuquidar (intraperitoneal injection; 30 mg/kg; once daily; 5 d) treatment shows the potentiation with a combined of Doxorubicin.

Key Properties

• CAS Number: 167465-36-3
• MW: 636.9871
• Purity: >98% (HPLC)
• Formula: C₃₂H₃₄Cl₃F₂N₃O₂
• SMILES: FC1([C@H]2[C@@H]1C3=C([C@@H](C4=CC=CC=C42)N5CCN(CC5)C[C@H](COC6=C7C=CC=NC7=CC=C6)O)C=CC=C3)F.Cl.Cl.Cl
• Target: P-glycoprotein
• Solubility: 10 mM in DMSO

Bioactivity

• In Vivo:
  Zosuquidar (intraperitoneal injection; 30, 10, 3, or 1 mg/kg; once daily; 5 d) treatment shows a significant increase in life span. Zosuquidar (intraperitoneal injection; 30 mg/kg; once daily; 5 d) treatment shows the potentiation with a combined of Doxorubicin. Animal model: Mice implanted with P388/ADR tumors. Dosage: 30, 10, 3, or 1 mg/kg. Administration: Intraperitoneal injection; 30, 10, 3, or 1 mg/kg; once daily; 5 days. Result: Exihibited a significantly increased survival compared to the group treated with Doxorubicin alone (P<0.001). Animal model: Mice implanted with P388 or P388/ADR murine leukemia cells. Dosage: 30 mg/kg. Administration: Intraperitoneal injection; 30 mg/kg; once daily; 5 days. Result: Observed significant antitumor activity against the MDR P388/ADR cell lines when mice were treated with a combined dose of 30 mg/kg LY335979 and 1 mg/kg Doxorubicin (P = 0.1).
• In Vitro:
  Zosuquidar (0.3 μM; 48 h) enhances the cytotoxicity of DNR (substrates for P-glycoproteins) in P-glycoproteins active cell lines. Zosuquidar (5-16 μM; 72 h) treatment alone shows high cytotoxic concentration to drug-sensitive and MDR cell lines. ll Cytotoxicity Assay Cell line: K562 and HL60 cells. Concentration: 0.3 μM Incubation time: 48 hours. Result: Enhanced the cytotoxicity of DNR (substrates for P-glycoproteins) in K562/DOX cells more than 45.5-fold. Cell Cytotoxicity Assay Cell line: CCRF-CEM, CEM/VLB100, P388, P388/ADR, MCF7, MCF7/ADR, 2780, 2780AD, UCLA-P3, UCLA-P3.003VLB cells Concentration: 5-16 μM. Incubation time: 72 hours. Result: Showed IC50s of 6, 7, 15, 8, 7, 15, 11, 16, >5, >5 μM for CCRF-CEM, CEM/VLB100, P388, P388/ADR, MCF7, MCF7/ADR, 2780, 2780AD, UCLA-P3, UCLA-P3.003VLB cells, respectively.

Storage & Handling

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

Alternative Names

LY-335979 trihydrochloride

Quick Database Links

Gene Symbol

P-glycoprotein