标签归档：zosuquidar

Zosuquidar trihydrochloride(Synonyms: 唑喹达三盐酸盐; RS 33295-198 trihydrochloride; LY-335979 trihydrochloride)

发表于由

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

Zosuquidar trihydrochloride (Synonyms: 唑喹达三盐酸盐; RS 33295-198 trihydrochloride; LY-335979 trihydrochloride) 纯度: 99.79%

Zosuquidar (RS 33295-198) trihydrochloride 是 P-糖蛋白 (P-glycoprotein) 抑制剂，Ki 值为 59 nM。

Zosuquidar trihydrochloride(Synonyms: 唑喹达三盐酸盐; RS 33295-198 trihydrochloride; LY-335979 trihydrochloride)

Zosuquidar trihydrochloride Chemical Structure

CAS No. : 167465-36-3

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100 mg ￥9500 In-stock
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生物活性

Zosuquidar (RS 33295-198) trihydrochloride is an inhibitor of P-glycoprotein with a Ki value of 59 nM.

IC50 & Target

Ki: 59nM (P-glycoprotein)[1].
体外研究
(In Vitro)

Zosuquidar completely or partially restores drug sensitivity in all P-gp-expressing leukemia cell lines and enhances the cytotoxicity of anthracyclines (daunorubicin, idarubicin, mitoxantrone) and gemtuzumab ozogamicin (Mylotarg) in primary AmL blasts with active P-gp. In addition, P-gp inhibition by zosuquidar is found to be more potent than cyclosporine A in cells with highly active P-gp[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
体内研究
(In Vivo)

Zosuquidar trihydrochloride is only moderately active as an inhibitor of P-gp at the blood-brain. An oral dose of 25 mg/kg of zosuquidar trihydrochloride increases the brain concentrations by about 2.5-fold at 1 h and 5-fold at 24 h after paclitaxel administrationbarrier[3]. Zosuquidar enhances the brain uptake of nelfinavir in a dose-dependent manner. Brain tissue/plasma nelfinavir concentration ratios increase from 0.06±0.03 in the absence of zosuquidar administration and 0.09±0.02 between 2 and 6 h after a 2 mg/kg intravenous dose of zosuquidar to 0.85±0.19 after 6h and 1.58±0.67 after 20 mg/kg zosuquidar[4].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Clinical Trial

分子量

636.99

Formula

C32H34Cl3F2N3O2
CAS 号

167465-36-3
中文名称

唑喹达三盐酸盐
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式

4°C, sealed storage, away from moisture

*该产品在溶液状态不稳定，建议您现用现配，即刻使用。
溶解性数据
In Vitro: 

H2O : 5 mg/mL (7.85 mM; Need ultrasonic)

DMSO : 1 mg/mL (1.57 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.5699 mL 7.8494 mL 15.6988 mL
5 mM 0.3140 mL 1.5699 mL 3.1398 mL
10 mM — — —

*

请根据产品在不同溶剂中的溶解度，选择合适的溶剂配制储备液；该产品在溶液状态不稳定，建议您现用现配，即刻使用。

In Vivo:
  • 1.

    Zosuquidar is dissolved in 20% ethanol-saline[5].
参考文献

  • [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]. 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.

    [3]. Tang R, et al. Zosuquidar?restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AmL). BMC Cancer.?2008 Feb 13;8:51.?

    [4]. 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.

    [5]. 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.
Cell Assay
[2]

Cells are cultured in 96-well plates. Each drug of interest is added at escalating concentrations in the presence or absence of either zosuquidar or CsA. After 48 hour incubation (except Mylotarg, 4 days incubation), 20 μL of MTT is added to each well for a further 4 hour incubation. The purple precipitate is dissolved in 200 μL DMSO, and the optic density (OD) is determined by the multi-well plate reader[2].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Administration
[3][4]

Rats: Female Sprague-Dawley rats are used in the study. Zosuquidar solutions are prepared in 5% mannitol and adjusted to pH ～2.0 with concentrated HCl. Nelfinavir is infused (10 mg/kg/h) for up to 10 h with or without concurrent administration of an intravenous bolus dose of 2, 6, or 20 mg/kg zosuquidar given at 4 h. Brain tissue and plasma are analyzed for both drug concentrations[4].

Mice: A stock solution of 5 mg/mL of zosuquidar trihydrochloride is prepared in vehicle solution and diluted in sterile saline. The vehicle solution consisted of 20 g/l mannitol and 1.5 g/l of glycine in water for injection and adjusted to a pH of 2.7 with hydrochloric acid. P-gp knockout mice and wild type mice are used as a model for complete inhibition of P-gp. Zosuquidar trihydrochloride is administered orally at 25 and 80 mg/kg 1 h before i.v. paclitaxel and i.v. at 20 mg/kg 10 min and 1 h before paclitaxel. The concentrations of paclitaxel in plasma and tissues and of zosuquidar trihydrochloride in plasma are quantified by high-performance liquid chromatography[3].

上海金畔生物科技有限公司 has not independently confirmed the accuracy of these methods. They are for reference only.
参考文献

  • [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]. 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.

    [3]. Tang R, et al. Zosuquidar?restores drug sensitivity in P-glycoprotein expressing acute myeloid leukemia (AmL). BMC Cancer.?2008 Feb 13;8:51.?

    [4]. 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.

    [5]. 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.

所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务

Zosuquidar(Synonyms: RS 33295-198; LY-335979)

发表于由

上海金畔生物科技有限公司为生命科学和医药研发人员提供生物活性分子抑制剂、激动剂、特异性抑制剂、化合物库、重组蛋白，专注于信号通路和疾病研究领域。

Zosuquidar (Synonyms: RS 33295-198; LY-335979)

Zosuquidar (LY335979) 是 P-糖蛋白 (P-glycoprotein) 抑制剂，Ki 值为 59 nM。

Zosuquidar(Synonyms: RS 33295-198; LY-335979)

Zosuquidar Chemical Structure

CAS No. : 167354-41-8

规格 是否有货
100 mg   询价  
250 mg   询价  
500 mg   询价  

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Zosuquidar 的其他形式现货产品:

Zosuquidar trihydrochloride

生物活性

Zosuquidar (LY335979) is an inhibitor of P-glycoprotein with a Ki value of 59 nM.

Clinical Trial

分子量

527.60

Formula

C32H31F2N3O2
CAS 号

167354-41-8
运输条件

Room temperature in continental US; may vary elsewhere.
储存方式
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
溶解性数据
In Vitro: 

DMSO : 8.33 mg/mL (15.79 mM; Need ultrasonic)

配制储备液
浓度 溶剂体积 质量 1 mg 5 mg 10 mg
1 mM 1.8954 mL 9.4769 mL 18.9538 mL
5 mM 0.3791 mL 1.8954 mL 3.7908 mL
10 mM 0.1895 mL 0.9477 mL 1.8954 mL

*

请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80°C, 6 months; -20°C, 1 month。-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。

In Vivo:

请根据您的实验动物和给药方式选择适当的溶解方案。以下溶解方案都请先按照 In Vitro 方式配制澄清的储备液，再依次添加助溶剂：

——为保证实验结果的可靠性，澄清的储备液可以根据储存条件，适当保存；体内实验的工作液，建议您现用现配，当天使用； 以下溶剂前显示的百
分比是指该溶剂在您配制终溶液中的体积占比；如在配制过程中出现沉淀、析出现象，可以通过加热和/或超声的方式助溶

  • 1.

    请依序添加每种溶剂： 10% DMSO    40% PEG300    5% Tween-80    45% saline

    Solubility: ≥ 0.83 mg/mL (1.57 mM); Clear solution

    此方案可获得 ≥ 0.83 mg/mL (1.57 mM，饱和度未知) 的澄清溶液。

    以 1 mL 工作液为例，取 100 μL 8.3 mg/mL 的澄清 DMSO 储备液加到 400 μL PEG300 中，混合均匀；向上述体系中加入50 μL Tween-80，混合均匀；然后继续加入 450 μL生理盐水定容至 1 mL。

    将 0.9 g 氯化钠，完全溶解于 100 mL ddH₂O 中，得到澄清透明的生理盐水溶液

  • 2.

    请依序添加每种溶剂： 10% DMSO    90% (20% SBE-β-CD in saline)

    Solubility: 0.83 mg/mL (1.57 mM); Suspended solution; Need ultrasonic

    此方案可获得 0.83 mg/mL (1.57 mM) 的均匀悬浊液，悬浊液可用于口服和腹腔注射。

    以 1 mL 工作液为例，取 100 μL 8.3 mg/mL 的澄清 DMSO 储备液加到 900 μL 20% 的 SBE-β-CD 生理盐水水溶液中，混合均匀。

    将 2 g 磺丁基醚 β-环糊精加入 5 mL 生理盐水中，再用生理盐水定容至 10 mL，完全溶解，澄清透明
  • 3.

    请依序添加每种溶剂： 10% DMSO    90% corn oil

    Solubility: ≥ 0.83 mg/mL (1.57 mM); Clear solution

    此方案可获得 ≥ 0.83 mg/mL (1.57 mM，饱和度未知) 的澄清溶液，此方案不适用于实验周期在半个月以上的实验。

    以 1 mL 工作液为例，取 100 μL 8.3 mg/mL 的澄清 DMSO 储备液加到 900 μL玉米油中，混合均匀。

*以上所有助溶剂都可在 上海金畔生物科技有限公司 网站选购。
参考文献

  • [1]. Dantzig AH, et al. Reversal of P-glycoprotein-mediated multidrug resistance by a potent cyclopropyldibenzosuberane modulator, LY335979. Cancer Res. 1996 Sep 15;56(18):4171-9.

    [2]. Marcelletti JF, Multani PS, Lancet JE et al. Leukemic blast and natural killer cell P-glycoprotein function and inhibition in a clinical trial of zosuquidar infusion in acute myeloid leukemia. Leuk Res. 2009 Jun;33(6):769-74.

    [3]. Ruff P, Vorobiof DA, Jordaan JP et al. A randomized, placebo-controlled, double-blind phase 2 study of docetaxel compared to docetaxel plus zosuquidar (LY335979) in women with metastatic or locally recurrent breast cancer who have received one prior chemotherapy regimen. Cancer Chemother Pharmacol. 2009 Sep;64(4):763-8.

    [4]. Cripe LD, Uno H, Paietta EM 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. 2010 Nov 18;116(20):4077-85.

    [5]. Abu Ajaj K, Graeser R, Kratz F. Zosuquidar and an albumin-binding prodrug of zosuquidar reverse multidrug resistance in breast cancer cells of doxorubicin and an albumin-binding prodrug of doxorubicin. Breast Cancer Res Treat. 2012 Jul;134(1):117-29.

所有产品仅用作科学研究或药证申报，我们不为任何个人用途提供产品和服务