生物活性
Geldanamycin是一种天然的HSP90抑制剂，Kd为1.2 μM，特异性干扰糖皮质激素受体（GR）/HSP联合。Geldanamycin induces the degradation of proteins that are mutated in tumor cells such as v-Src, Bcr-Abl and p53 preferentially over their normal cellular counterparts. This effect is mediated via HSP90. Despite its potent antitumor potential, geldanamycin presents several major drawbacks as a drug candidate (namely, hepatotoxicity) that have led to the development of geldanamycin analogues, in particular analogues containing a derivatisation at the 17 position:17-AAG,17-DMAG.
化学数据
| 分子量 | 560.64 |
| 分子式 | C29H40N2O9 |
| CAS号 | 30562-34-6 |
| 纯度 | 99.84% |
| 溶解性（25°C） | DMSO: ≥ 19 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 | A2780 human ovarian cell line |
| 方法 | Treating exponentially growing cells with Geldanamycin and assessing at various times DNA synthesis by incorporation of bromodeoxyuridine (BrdUrd) and flow cytometric analysis. No marked difference in total cell number is noted during this time course for treated and untreated cultures. BrdUrd (10 μM) is incorporated over a 4-h incubation period at 37 °C and cells are harvested and fixed in 70% ethanol. After denaturation of the DNA with 2 N HC1, incubating cells with an anti-BrdUrd mouse monoclonal antibody followed by a fluorescein isothiocyanate (FITC)-linked goat anti-mouse IgG. Staining cells for 30 minutes at room temperature with propidium iodide and analysing by flow cytometry using a Coulter EPICS Profile Analyzer.
|
| 浓度 | 0.001-10 μM |
| 处理时间 | 3 hours |
| 动物实验 |
|---|
| 动物模型 | FRE/erbB-2 tumors in nu/nu mice |
| 配制 | Geldana50 mg/kgmycin is dissolved in DMSO. |
| 剂量 | 50 mg/kg |
| 给药处理 | Administered via i.p. |
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 | 1.7837 mL | 8.9184 mL | 17.8368 mL |
| 5 mM | 0.3567 mL | 1.7837 mL | 3.5674 mL |
| 10 mM | 0.1784 mL | 0.8918 mL | 1.7837 mL |
