Topotecan HCl
(Synonyms: 盐酸拓扑替康; SKF 104864A Hydrochloride; NSC 609669 Hydrochloride) 目录号 : GC13359
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Topotecan HCl是一种毒药类的拓扑异构酶I抑制剂。
Cas No.:119413-54-6
Sample solution is provided at 25 µL, 10mM.
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Topotecan HCl is a topoisomerase I inhibitor that acts as a Topo I poison. Topotecan HCl specifically targets the topoisomerase I–DNA cleavage complex, acting after DNA cleavage and inhibiting the re-ligation step. Topotecan HCl can cross the blood–brain barrier and exhibits cytotoxicity against a variety of tumor cell types, showing significant activity in the treatment of brain tumors[1].
In vitro, Topotecan HCl (0.02-40μM; 12-48h) dose- and time-dependently inhibited the proliferation of U251, U87, GSCs-U251, and GSCs-U87 cells, with IC₅₀ values at 24h of 2.73±0.25, 2.95±0.23, 5.46±0.41, and 5.95±0.24μM, respectively[1]. Topotecan HCl (3μM; 24h) significantly upregulated p21 protein levels and induced cell cycle arrest at the G0/G1 and S phases in U251, U87, GSCs-U251, and GSCs-U87 cells[1]. Topotecan HCl (0.1-1000ng/mL; 72h) caused a dose-dependent reduction in the viability of HUVECs, with an IC₅₀ of 4.87ng/mL[2]. Among neuroblastoma cell lines, the IC50 values of Topotecan HCl on SH-SY5Y, BE(2)-c and SK-N-BE(2) were 5.3ng/mL, 45.6ng/mL and 65.0ng/mL, respectively. Among sarcoma cell lines, the IC50 values of Topotecan HCl on RH30, RD, and KHOS cell lines were 7.4ng/mL, 7.5ng/mL, and 4.9ng/mL, respectively[2].
In vivo, Topotecan HCl (1mg/kg/d; p.o.; 56d) significantly improved the survival of nonobese diabetic/severe combined immune deficient (NOD/SCID) mice bearing SK-N-BE (2)[2]. In IGROV-1 tumour-bearing mice, Topotecan HCl (10mg/kg) given intraperitoneally every 4 days for four occasions markedly increased survival time over control mice[3].
References:
[1] Zhang FL, Wang P, Liu YH, et al. Topoisomerase I inhibitors, shikonin and Topotecan HCl, inhibit growth and induce apoptosis of glioma cells and glioma stem cells. PLoS One. 2013;8(11):e81815.
[2] Kumar S, Mokhtari RB, Sheikh R, et al. Metronomic oral Topotecan HCl with pazopanib is an active antiangiogenic regimen in mouse models of aggressive pediatric solid tumor. Clin Cancer Res. 2011;17(17):5656-5667.
[3] Pratesi G, Tortoreto M, Corti C, Giardini R, Zunino F. Successful local regional therapy with Topotecan HCl of intraperitoneally growing human ovarian carcinoma xenografts. Br J Cancer. 1995;71(3):525-528.
Topotecan HCl是一种毒药类的拓扑异构酶I抑制剂。Topotecan HCl特异性靶向拓扑异构酶I-DNA切割复合体，在DNA切割后起作用并抑制再重组。Topotecan HCl可以穿过血脑屏障，对多种肿瘤细胞表现出细胞毒性，在脑肿瘤治疗中显示出显著的活性[1]。
体外实验中，Topotecan HCl（0.02-40μM；12-48h）以剂量和时间依赖方式抑制U251，U87，GSCs-U251和GSCs-U87细胞的增殖，处理24小时的IC₅₀值分别为2.73±0.25，2.95±0.23，5.46±0.41和5.95±0.24μM[1]。Topotecan HCl（3μM；24h）显著上调U251，U87，GSCs-U251和GSCs-U87细胞中p21蛋白水平，并诱导细胞周期阻滞于G0/G1期和S期[1]。Topotecan HCl（0.1-1000ng/mL；72h）以剂量依赖方式降低HUVECs细胞的活力，其IC₅₀值为4.87ng/mL[2]。在神经母细胞瘤细胞系中，Topotecan HCl对SH-SY5Y，BE(2)-c和SK-N-BE(2)的IC50值分别为5.3ng/mL，45.6ng/mL和65.0ng/mL。在肉瘤细胞系中，Topotecan HCl对RH30、RD和KHOS细胞系的IC50值分别为7.4ng/mL，7.5ng/mL和4.9ng/mL[2]。
体内实验中，Topotecan HCl（1mg/kg/天；口服；连续56天）显著提高了携带SK-N-BE(2)肿瘤的NOD/SCID小鼠的生存率[2]。在IGROV-1荷瘤小鼠中，10mg/kg的Topotecan HCl腹腔内每4天给药一次，共4次，小鼠生存时间明显增加[3]。
| Cell experiment [1]: | |
Cell lines | U251, U87, GSCs-U251, GSCs-U87 cells |
Preparation Method | U251, U87, GSCs-U251 and GSCs-U87 cells were treated with different concentrations of Topotecan HCl for 24h, and cell viability were assayed by CCK-8. |
Reaction Conditions | 0.02, 0.2, 2, 20, 40μM ; 24h |
Applications | The cell viability was inhibited by Topotecan HCl in a dose-dependent manner. The IC50 values of Topotecan HCl at 24h were 2.73±0.25μM of U251 cells, 2.95±0.23μM of U87 cells, 5.46±0.41μM of GSCs-U251 and 5.95±0.24μM of GSCs-U87. |
| Animal experiment [2]: | |
Animal models | Nonobese diabetic/severe combined immune deficient (NOD/SCID) mice bearing SK-N-BE(2) |
Preparation Method | When tumors reached 0.5cm in diameter, the animals were randomized into 4 groups and treated daily by oral gavage. The animals were grouped as: Control group, Topotecan HCl group (1.0mg/kg), Pazopanib group (150mg/kg) and Topotecan HCl+Pazopanib group (1.0mg/kg+150mg/kg). Drugs were administered daily over a period of 56 days. The animals belonging to the Topotecan HCl+Pazopanib group, which remained alive, were also retreated from the 103rd day to evaluate the impact of resuming treatment on reversing drug resistance. Retreatment was continued until the 125th day, after which the mice were sacrificed. |
Dosage form | 1.0mg/kg/d; 56 or 56+23d; p.o. |
Applications | Compared with control, both the single agents significantly enhanced survival of animals. The survival in Topotecan HCl+Pazopanib group was significantly higher compared with both control |
References: | |
| Cas No. | 119413-54-6 | SDF | |
| 别名 | 盐酸拓扑替康; SKF 104864A Hydrochloride; NSC 609669 Hydrochloride | ||
| 化学名 | (S)-10-((dimethylamino)methyl)-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione hydrochloride | ||
| Canonical SMILES | Cl[H].O=C1N(C([H])([H])C2=C([H])C(C(C([H])([H])N(C([H])([H])[H])C([H])([H])[H])=C3O[H])=C(C([H])=C3[H])N=C42)C4=C([H])C([C@@](C([H])([H])C([H])([H])[H])5O[H])=C1C([H])([H])OC5=O | ||
| 分子式 | C23H24ClN3O5 | 分子量 | 457.91 |
| 溶解度 | ≥ 22.9mg/mL in DMSO | 储存条件 | 4°C, protect from light |
| General tips | 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 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.1838 mL | 10.9192 mL | 21.8384 mL |
| 5 mM | 436.8 μL | 2.1838 mL | 4.3677 mL |
| 10 mM | 218.4 μL | 1.0919 mL | 2.1838 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
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工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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- Purity: >99.00% Appearance: A solid
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