Zosuquidar
产品说明书
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同义名 : | 佐舒奎达 ;RS 33295-198; LY-335979 |
| CAS号 : | 167354-41-8 | |
| 货号 : | A364386 | |
| 分子式 : | C32H31F2N3O2 | |
| 纯度 : | 99+% | |
| 分子量 : | 527.6 | |
| MDL号 : | MFCD09837761 | |
| 存储条件： |
Pure form Inert atmosphere, store in freezer, under -20°C In solvent -20°C:3-6个月-80°C:12个月 |
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| 溶解度 : |
DMSO: 4 mg/mL(7.58 mM)，配合低频超声，水浴加热至45℃，并调节pH至2，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 |
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| 动物实验配方： |
| 生物活性 | |||
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| 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 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 | - | Completed | - | - | |
| NCT00046930 | Leukemia Myel... 展开 >>odysplastic Syndromes 收起 << | Phase 3 | Completed | - | - |
| NCT00129168 | Leukemia, Myeloid | Phase 1 Phase 2 | Completed | - | - |
| 实验方案 | |||
|---|---|---|---|
| 1mg | 5mg | 10mg | |
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1 mM 5 mM 10 mM |
1.90mL 0.38mL 0.19mL |
9.48mL 1.90mL 0.95mL |
18.95mL 3.79mL 1.90mL |
| 参考文献 |
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