Topotecan是一种毒药类的拓扑异构酶I抑制剂。
Cas No.:123948-87-8
Sample solution is provided at 25 µL, 10mM.
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Topotecan is a topoisomerase I inhibitor that acts as a Topo I poison. Topotecan specifically targets the topoisomerase I–DNA cleavage complex, acting after DNA cleavage and inhibiting the re-ligation step. Topotecan 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 (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 (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 (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 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 on RH30, RD, and KHOS cell lines were 7.4ng/mL, 7.5ng/mL, and 4.9ng/mL, respectively[2].
In vivo, Topotecan (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 (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, 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 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 of intraperitoneally growing human ovarian carcinoma xenografts. Br J Cancer. 1995;71(3):525-528.
Topotecan是一种毒药类的拓扑异构酶I抑制剂。Topotecan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（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（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（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（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 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 in a dose-dependent manner. The IC50 values of Topotecan 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 group (1.0mg/kg), Pazopanib group (150mg/kg) and Topotecan+Pazopanib group (1.0mg/kg+150mg/kg). Drugs were administered daily over a period of 56 days. The animals belonging to the Topotecan+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+Pazopanib group was significantly higher compared with both control |
References: | |
| Cas No. | 123948-87-8 | SDF | |
| 别名 | 拓扑替康; SKF 104864A; NSC 609669 | ||
| 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 | ||
| Canonical SMILES | CC[C@]1(O)C(C=C2C3=NC4=CC=C(O)C(CN(C)C)=C4C=C3CN2C5=O)=C5COC1=O | ||
| 分子式 | C23H23N3O5 | 分子量 | 421.45 |
| 溶解度 | ≥ 21.1mg/mL in DMSO | 储存条件 | Store at -20°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 | 2.3728 mL | 11.8638 mL | 23.7276 mL |
| 5 mM | 474.6 μL | 2.3728 mL | 4.7455 mL |
| 10 mM | 237.3 μL | 1.1864 mL | 2.3728 mL |
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| 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 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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