Zosuquidar trihydrochloride

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

一种有效的 P-糖蛋白 (P-gp) 抑制剂，Ki 为 60 nM。

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.

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.

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).

LY-335979 trihydrochloride

Membrane Transporter/Ion Channel

P-glycoprotein

P-gp?(P-glycoprotein)

Cancer

Blood cancer

167465-36-3

636.9871

C32H34Cl3F2N3O2

>98% (HPLC)

10 mM in DMSO

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

1-Piperazineethanol, 4-[(1a.alpha.,6.alpha.,10b.alpha.)-1,1-difluoro-1,1a,6,10b-tetrahydrodibenzo[a,e]cyclopropa[c]cyclohepten-6-yl]-.alpha.-[(5-quinolinyloxy)methyl]-, hydrochloride (1:3), (.alpha.R)-

(-20℃)

With Ice Pack

≥ 2 years