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Zosuquidar 3HCl

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Chemical Structure| 167465-36-3 同义名 : LY-335979 trihydrochloride;RS 33295-198 trihydrochloride;RS 33295-198;LY335979;Zosuquidar (hydrochloride);D06387 3HCl;RS 33295-198 3HCl;LY335979 3HCl;Zosuquidar trihydrochloride
CAS号 : 167465-36-3
货号 : A272992
分子式 : C32H34Cl3F2N3O2
纯度 : 99%+
分子量 : 636.987
MDL号 : MFCD00942300
存储条件：

粉末 Inert atmosphere,Room Temperature

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 1 mg/mL(1.57 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO

H2O: 5 mg/mL(7.85 mM)，配合低频超声助溶
动物实验配方：
生物活性
靶点

  • P-gp

    P-gp, Ki:60 nM
描述 The multidrug resistance is an obstacle in the chemotherapy treatment (such as doxorubicin, vincristine, paclitaxel, TKIs) for many solid and haematological tumours. Many factors can cause the multidrug resistance. Among them, the overexpression of P-gp (ABCB1), an ATP-binding cassette (ABC) drug efflux transporter, on the surface of resistant cells is considered as a key factor mediating multidrug resistance. Zosuquidar Trihydrochloride is the trihydrochloride form of Zosuquidar. Zosuquidar is P-gp modulator that inhibited Pgp-ATPase activity 50-60% at 2 and 10μM and had no effect at 0.08 and 0.4μM (measured by P-gp ATPase activity). However, the modulator activity of Zosuquidar is not dependent on inhibition of the ATPase activity associated with P-gp. Zosuquidar works both in vitro and in vivo. Combined treatment with Zosuquidar at 0.1μM could fully restored sensitivity of CEM/VLB100 cells to vinblastine, doxorubicin, etoposide and Taxol, and showed a prolonged effect up to 24h at concentration of 0.5μM in cytotoxicity assay of doxorubicin. The effect of Zosuquidar on restoring sensitivity of different compound may due to its blocking the affinity of compound to cell plasma membranes P-gp and competitively inhibited equilibrium binding of compound to P-gp (Ki=~60nM). Co-administration of Zosuquidar (20mg/kg, i.v.) with doxorubicin or etoposide significantly increased the life span of mice bearing P388/ADR murine leukemia cells, compared with group treated with agent alone. Also Zosuquidar (30mg/kg) enhanced the antitumor activity of Taxol in a multidrug-resistant human non-small cell lung carcinoma nude mouse xenograft model. However this in vivo increased life span achieved by Zosuquidar was lack of effect on pharmacokinetics[1].
临床研究
NCT号 适应症或疾病 临床期 招募状态 预计完成时间 地点
NCT00046930 Leukemia Myel... 展开 >>odysplastic Syndromes 收起 << Phase 3 Completed - -
NCT00046930 - Completed - -
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

1.57mL

0.31mL

0.16mL

7.85mL

1.57mL

0.78mL

15.70mL

3.14mL

1.57mL
参考文献

[1]Dantzig AH, Shepard RL, 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]Kemper EM, Cleypool C, et al. The influence of the P-glycoprotein inhibitor zosuquidar trihydrochloride (LY335979) on the brain penetration of paclitaxel in mice. Cancer Chemother Pharmacol. 2004;53(2):173-8.

[3]Anderson BD, May MJ, 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. Epub 2006 Jan 24.