CAS |
167465-36-3 |
Chinese Name |
唑喹达三盐酸盐 |
English Name |
Zosuquidar triHydrochloride |
Synonyms |
LY-335979trihydrochloride;RS33295-198trihydrochloride |
Molecular Formula |
C32H31F2N3O2·3HCl |
Molecular Weight |
636.99 |
Solubility |
Soluble in Water ≥1mg/mL(Need ultrasonic or Water bath) |
Purity |
≥98% |
Appearance |
Light yellow to yellow Solid |
Storage |
Powder:2-8℃,2 years;Insolvent(Mother Liquid):-20℃,6 months;-80℃,1 year |
MDL |
MFCD00942300 |
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 Point |
P-gp(P-glycoprotein) |
Passage |
Membrane Transporter&Ion Channel |
Background |
Zosuquidar trihydrochloride is an inhibitor of P-glycoprotein. |
Biological Activity |
Zosuquidar trihydrochloride是P-糖蛋白(P-gp)的抑制剂, Ki值为59 nM。[1-5] |
In Vitro |
Zosuquidar完全或部分恢复所有表达P-gp的白血病细胞系中的药物敏感性,并增强蒽环霉素(柔红霉素,伊达比星,米托蒽醌)和吉妥珠单抗奥佐米星(Mylotarg)在具有活性P-gp的原代AmL母细胞中的细胞毒性。此外,在具有高活性P-gp的细胞中,zosuquidar对P-gp的抑制作用比环孢菌素A更强[2]。 |
In Vivo |
Zosuquidar trihydrochloride仅作为血脑中P-gp的抑制剂具有中等活性。口服剂量为25 mg/kg的zosuquidar trihydrochloride在紫杉醇给药屏障后1小时和25小时后脑浓度增加约2.5倍[3]。 Zosuquidar以剂量依赖的方式增强大脑对奈非那韦的摄取。在没有zosuquidar给药的情况下,脑组织/血浆奈非那韦浓度比从0.06±0.03增加,在2mg/kg静脉注射zosuquidar后2和6小时之间增加0.09±0.02,在6h后增加到0.85±0.19,在20mg后增加到1.58±0.67/kg zosuquidar [4]。 |
Cell Experiment |
将细胞在96孔板中培养。在存在或不存在zosuquidar或CsA的情况下,以逐步升高的浓度添加每种感兴趣的药物。孵育48小时后(除Mylotarg,孵育4天),向每个孔中加入20μLMTT,再孵育4小时。将紫色沉淀溶解在200μLDMSO中,并通过多孔板读数器测定光密度(OD)[2]。 |
Animal Experiment |
大鼠:雌性Sprague-Dawley大鼠用于该研究。 Zosuquidar溶液在5%甘露醇中制备,并用浓HCl调节至pH~2.0。将奈非那韦输注(10mg/kg/h)长达10小时,同时或不同时施用静脉推注剂量的2,6或20mg/kg zosuquidar,在4小时给予。分析两种药物浓度的脑组织和血浆[4]。小鼠:在载体溶液中制备5mg/mL的zosuquidar三盐酸盐的储备溶液,并在无菌盐水中稀释。载体溶液由20g/l甘露醇和1.5g/l甘氨酸水溶液组成,用盐酸调节至pH2.7。将P-gp敲除小鼠和野生型小鼠用作完全抑制P-gp的模型。 Zosuquidar三盐酸盐在静脉注射紫杉醇之前1小时以25和80mg/kg口服给药,并且在紫杉醇之前10分钟和1小时以20mg/kg静脉内给药。通过高效液相色谱法定量测定血浆和组织中紫杉醇的浓度和血浆中的盐酸zosuquidar三盐酸盐的浓度[3]。 |
Data Literature Source |
[1]. Cripe LD,et al. Zosuquidar,a novel modulator of P-glycoprotein,does not improve the outcome of older patients with newly diagnosed acute myeloid leukemia: a randomized,placebo-controlled trial of the Eastern Cooperative Oncology Group 3999. Blood. 201 [2]. Tang R,et al. Zosuquidar restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AmL). BMC Cancer. 2008 Feb 13;8:51. [3]. Kemper EM,et al. The influence of the P-glycoprotein inhibitor zosuquidar trihydrochloride (LY335979) on the brain penetration of paclitaxel in mice. Cancer Chemother Pharmacol. 2004 Feb;53(2):173-8. [4]. Anderson BD,et al. Dependence of nelfinavir brain uptake on dose and tissue concentrations of the selective P-glycoprotein inhibitor zosuquidar in rats. Drug Metab Dispos. 2006 Apr;34(4):653-9. [5]. Hou J,et al. Quantitative determination and pharmacokinetic study of the novel anti-Parkinson's disease candidate drug FLZ in rat brain by high performance liquid chromatography-tandem mass spectrometry. J Pharm Biomed Anal. 2012 Jul;66:232-9. |
Unit |
Bottle |
Specification |
5mg 10mg 50mg |