生物活性
Zosuquidar (LY335979) 3HCl是一种有效的P-glycoprotein（P-糖蛋白）介导的多药耐抗性的调节剂，Ki为60 nM。LY335979 竞争性抑制[3H]vinblastine与P-gp的平衡结合，Ki为 60 nM，通过阻断CEM/VLB100质膜中P-gp的[3H]azidopine的光亲和标记。LY335979 浓度为0.1 μM时，单独给药对药物敏感的MDR细胞系，具有细胞毒性，IC50为6 μM-16 μM，且浓度为 0.5 μM时，完全扭转对 MDR 细胞P388/ADR, MCF7/ADR, 2780AD, 或 UCLA-P3.003VLB溶瘤细胞抗性(Vinblastine, Doxorubicin, 或 Etoposide)。LY335979作用于表达P-gp的白血病细胞系，包括K562/HHT40, K562/HHT90, K562/DOX 和 HL60/DNR，显著恢复药物敏感性，且作用于携带活性P-gp的原发性AML细胞，增强蒽环类药物(Daunorubicin, Idarubicin, Mitoxantrone)和gemtuzumab ozogamicin 的毒性。
化学数据
| 分子量 | 637.00 |
| 分子式 | C32H31F2N3O2.3HCl |
| CAS号 | 167465-36-3 |
| 纯度 | 99.46% |
| 溶解性（25°C） | DMSO ≥35 mg/mL |
| 储存和运输条件 | 固体粉末： -20°C 冷藏长期储存
常温运输及临时存放 |
实验操作 来自于公开的文献，仅供相同实验参考（如实验材料、目的不同，请参考其他文献）
| 细胞实验 |
|---|
| 细胞系 | MCF-7 and MCF-7/ADR cells |
| 方法 | Cytotoxicity Assays.
Cell viability was determined using a modified 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction method. Cells were harvested during logarithmic growth phase, and seeded in 96-well plates (Costar) at 7.5X104cells/well. The cells were then cultured for 72 h in the presence of oncolytics with or without modulators. MCF-7 and MCF-7/ADR cells were incubated 24 h before the addition of the drug with and without the modulator. Modulators were prepared as 2 mM DMSO stocks and added to wells to give final concentrations ranging from 0.05 to 5 uM. After 72 h, 20 ul of freshly prepared 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyltetrazolium bromide (5 mg/mL in Dulbecco's PBS) was added to each well and incubated for 4 h in a 37°C incubator containing 5% CO2. Cells were pelleted in a Sorvall RT6000B centrifuge, 70 p.1of medium was carefully removed from each well, and 100ul of 2-propanol/0.04 N HC1 was added. Cells were resuspended 5-10 times with a Multipipettor or until no particulate matter was visible. Plates were immediately read on a Titertek Multiskan MCC/340 microplate reader Flow Laboratories (McLean, VA) with a test wavelength of 570 nm and a reference wavelength of 630 nm.Controls were measured in quadruplicate and modulators were measured in duplicate. Cytotoxicity analyses were also performed using the CeliTiter 96 AQueous assay kit (Promega Corp., Madison, WI) according to the manufacturer's instructions. |
| 浓度 | 0.05~5μM |
| 处理时间 | 72h |
| 动物实验 |
|---|
| 动物模型 | P388/ADR tumors bearing mice |
| 配制 | stock solution was 2.5 to 5 mg/nil in 5% manrntol |
| 剂量 | 20 mg/kg once daily for 5 days |
| 给药处理 | i.v. injection |
不同实验动物依据体表面积的等效剂量转换表（数据来源于FDA指南）
| 小鼠 | 大鼠 | 兔 | 豚鼠 | 仓鼠 | 狗 |
| 重量 (kg) | 0.02 | 0.15 | 1.8 | 0.4 | 0.08 | 10 |
| 体表面积 (m2) | 0.007 | 0.025 | 0.15 | 0.05 | 0.02 | 0.5 |
| Km系数 | 3 | 6 | 12 | 8 | 5 | 20 |
| 动物 A (mg/kg) = 动物 B (mg/kg) × | 动物 B的Km系数 |
| 动物 A的Km系数 |
例如，依据体表面积折算法，将化合物用于小鼠的剂量20 mg/kg 换算成大鼠的剂量，需要将20 mg/kg 乘以小鼠的Km系数（3），再除以大鼠的Km系数（6），得到化合物用于大鼠的等效剂量为10 mg/kg。
储备液配制
以下数据基于产品分子量，对于特殊产品，请参照COA中的储备液配制条件和说明进行操作。
| Concentration / Solvent Volume / Mass | 1 mg | 5 mg | 10 mg |
|---|
| 1 mM | 1.5699 mL | 7.8493 mL | 15.6986 mL |
| 5 mM | 0.314 mL | 1.5699 mL | 3.1397 mL |
| 10 mM | 0.157 mL | 0.7849 mL | 1.5699 mL |
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