119413-54-6

• 常用中文名：盐酸拓扑替康
• 常用英文名：Topotecan hydrochloride
• CAS号：119413-54-6
• 分子式：C₂₃H₂₄ClN₃O₅
• 分子量：421.446
• 相关类别： 原料药 抗肿瘤药 天然来源类抗肿瘤药
• 发布时间：2018-06-30 11:14:23
• 更新时间：2026-07-01 19:08:18
• 【用途一】
  抗肿瘤药。

名称

• 中文名: 拓普替康
• 英文名: Topotecan HCl
• 中文别名: SKF 104864A|||SKFS 104864A|||NSC609699|||NOGITECAN HCL|||NSC 609669|||盐酸拓扑替康|||TOPOTECAN HCL; 盐酸拓扑替康/盐酸托泊替康; 盐酸拓普替康(替康类); TOPOTECAN HYDROCHLORIDE (SKF 104864),TOPOISOMERASE抑制剂; 鈦癩HENICOSA-1,2,3,5,7,9,15-HTAENE-14,18-DIONE HYDROCHLORIDE; (S)-10-((二甲胺基)甲基)-4-乙基-4,9-二羟基-1H-吡喃并[3',4':6,7]吲哚并[1,2-B]喹啉-3,14(4H,12H)-二酮盐酸盐; (S)-4-乙基-4,9-二羟基-10-[(二甲基氨基)甲基]-1H-吡喃并[3',4':6,7]吲嗪并[1,2-B]喹啉-3,14(4H,12H)-二酮盐酸盐; 盐酸拓扑替; 拓扑替康盐酸盐(标准品); 盐酸拓普替康; 反-3-氮杂二环[4.1.0]庚烷-2-羧酸盐酸; 盐酸托泊替康、盐酸拓扑替坎; SKF104864) 是靶向拓扑异构酶I的细胞毒性剂,已进入临床试验。; TOPOTECAN盐酸盐; 拓扑替康(盐酸); 盐酸拓扑特康、盐酸拓普替康; 盐酸拓补替康; 盐酸反-3,4-二甲氧基吡咯烷; (S)-10-[(二甲基氨基)甲基]-4-乙基-4,9-二羟基-1H-吡喃并[3',4':6,7]氮茚并[1,2-b]-喹啉-(4H,12H)-二酮盐酸盐; 盐酸氢氩胺; TOPOTECAN HYDROCHLORIDE 盐酸拓扑替康; 盐酸拓扑替康 Solbio/索莱宝 IT1030; 2-(2-氯 -4-吡啶基)吗啉; 反-4-甲基四氢呋喃-3-胺盐酸; (S)-10-[(二甲基氨基)甲基]-4-乙基-4,9-二羟基-1H-吡喃并[3',4':6,7]中氮茚并[1,2-B]-喹啉-(4H,12H)-二酮盐酸盐; 盐酸拓扑替康,10 MM DMSO 溶液; 拓扑异构酶I抑制剂; 盐酸拓扑替康对照品; 顺-3-氟环己烷-1-胺盐酸; 盐酸拓扑替康标准品; Topotecan HCl (Hycamtin) 10mM * 1mL in DMSO试剂
• 英文别名: (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 monohydrochloride; Topotecan (Hydrochloride); C-[5-(3-Chloro-phenyl)-[1,3,4]oxadiazol-2-yl]-methylamine; 1,4-di(4-benzyloxy-2-butynyl)piperazine; (2R)-2-amino-3-(3-methylimidazol-4-yl)propanoic acid; C-[5-(3-Methoxy-phenyl)-[1,3,4]oxadiazol-2-yl]-methylamine; C-(5-p-Tolyl-[1,3,4]oxadiazol-2-yl)-methylamine; (4S)-10-[(DIMETHYLAMINO)METHYL]-4-ETHYL-4,9-DIHYDROXY-1H-PYRANO[3',4',]INDOLIZINO[1,2-B]QUINOLINE-3,14(4H,12H)-DIONE; 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; (2S)-2-[[(2R)-2-amino-3-(1H-indol-3-yl)propanoyl]amino]-4-methylpentanamide; Benzyl-[1-(2-chloro-ethyl)-piperidin-3-yl]-amine; methyl 3-methyl-2-(methylamino)butanoate; 1H-Pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, 10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-, monohydrochloride, (S); 4,7-dimethoxy-2-methyl-3,4-dihydro-1H-isoquinoline; (2S)-2-(methylamino)-3-sulfanylpropanoic acid; (2R)-2-(methylamino)-3-sulfanylpropanoic acid; Topotecan Hydrochloride（TPT）; Topotecan, Hydrochloride Salt; 1H-Pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, 10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-, monohydrochloride, (4S)- (9CI); TOPOTECAN HCL; TOPOTECAN MONOHYDROCHLORIDE; 2-(3-Fluoro-benzylsulfanyl)-ethylamine; topetecan hydrochloride; (4S)-10-[(Dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3’,4’,]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione Hydrochloride; HYDROCHLORIDE; 1,4-di[4-(3-phenoxypropoxy)-2-butynyl]piperazine; MFCD00866235; N-methyl-5-azaspiro（2.3）hexane-2-cboxamide; Topotecan hydrocloride; Topotecan (Nogitecan) HCl; 1-Methyl-2-(3-methyl-pyrazol-1-yl)-ethylamine; Topotecan Hydrochloride(TECANS); (3,5-Dimethoxy-phenyl)-(1H-pyrazol-3-ylmethyl)-amine; TOPOTECAN HYDROCHLORIDE; C-[5-(3-Fluoro-phenyl)-[1,3,4]oxadiazol-2-yl]-methylamine; SKF-104864A; (S)-10-[(dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-(H-Pyrano[3' , 4':6,7]indolizino[1,2-b]quinoline-3,14[4H,12H]-dione monohydrochloride; 1,1-Dimethyl-2-(2-oxo-2-phenyl-ethyl)-isothiourea; (4S)-10-[(Dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione; S-(6-thioxo-1,6-dihydro-pyrimidin-4-yl)-isothiourea; 5-bromo-7-methoxy-1,2,3,4-tetrahydroisoquinoline-4,6-diol; Topotecan HCl (HycaMtin); (4S)-10-[(Dimethylamino)methyl]-4-ethyl-4,9-dihydroxy-1H-pyranoindolizino[1,2-b]quinoline-3,14(4H,12H)-dione, Hydrochloride, SKF-104864A; 4-(2-Oxo-butyl)-benzamidine; C-(5-m-Tolyl-[1,3,4]oxadiazol-2-yl)-methylamine; 3-Methoxy-5-Methyl-4-MethylaMino-htanoic acid tert-butyl ester; SKF-S 104864-A; 1,4-di(4-benzhydryloxy-2-butynyl)piperazine; 9-[(DIMETHYLAMINO)METHYL]-10-HYDROXY-(20S)-CAMPTOTHECIN, HCL; 2-Methyl-4-piperidino-butan-2-ol; Topotecan; {3-[4-(7H-Pyrrolo[2,3-d]pyrimidin-4-yl)-pyrazol-1-yl]-azetidin-3-yl}-acetonitrile; Topotecan hydrochloride(NSC-609699); 8-methoxy-7-methyl-3,4-dihydroisoquinoline; 5-PIPERAZIN-1-YL-BENZOFURAN-2-CBOXYLIC ACID ETHYL ESTER; Toputecan hydrochloride; SKFS 104864A; [2-(4-Methyl-piperazin-1-yl)-ethyl]-cbamic acid tert-butyl ester; 1-Methyl-4-(toluene-4-sulfonyl)-piperazine; 2-(3-Chloro-5-trifluoromethyl-pyridin-2-yl)-ethylamine; 9-[(Dimethylamino)methyl]-10-hydroxy-(20S)-camptothecin; (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

物化性质

• 密度: 1.5±0.1 g/cm3
• 沸点: 782.9±60.0 °C at 760 mmHg
• 熔点: 213-218ºC
• 分子式: C₂₃H₂₄ClN₃O₅
• 分子量: 421.446
• 闪点: 427.3±32.9 °C
• 精确质量: 421.163757
• PSA: 104.89000
• LogP: 1.08
• 外观性状: 白色结晶固体
• 蒸汽压: 0.0±2.8 mmHg at 25°C
• 折射率: 1.734
• 储存条件: Refrigerator

生物活性

• 描述: Topotecan Hydrochloride (SKF 104864A; NSC 609669) 是具有抗癌活性的 拓扑异构酶I 抑制剂。
• 相关类别:
  信号通路 >> 自噬 >> 自噬
  信号通路 >> 细胞周期/DNA损伤 >> 拓扑异构酶
  研究领域 >> 癌症
• 靶点:

  Topoisomerase I

• 体外研究: 拓扑替康(SKF 104864A)不仅以剂量和时间依赖的方式明显抑制人胶质瘤细胞和胶质瘤干细胞(GSCs)的增殖。根据24小时的IC 50值,选择3μM托泊替康(SKF 104864A)作为最佳给药浓度。此外,拓扑替康(SKF 104864A)诱导G0/G1期和S期细胞周期停滞并促进细胞凋亡。结果显示拓扑替康(SKF 104864A)以剂量依赖性方式抑制细胞活力。与对照组相比,2,20和40μM托泊替康(SKF 104864A)明显抑制细胞活力。拓扑替康(SKF 104864A)24小时的IC 50值为2.73±0.25μM的U251细胞,2.95±0.23μM的U87细胞,5.46±0.41μM的GSCs-U251和5.95±0.24μM的GSC-U87。因此,在随后的实验中选择3μM托泊替康(SKF 104864A)作为最佳给药浓度[1]。
• 体内研究: NUB-7转移模型,处理14天后处死属于所有4组的动物。与对照相比,TP + PZ处理的动物与PZ相比,低剂量节拍(LDM)托泊替康(SKF 104864A)和TP +帕唑帕尼(PZ)肝重显着降低。除了TP + PZ之外,在属于所有组的小鼠的肝脏中可见微观肿瘤,证实拓扑替康(SKF 104864A)+ PZ控制肝转移的能力。在先前的剂量反应研究中,与每周最大耐受剂量方案相比,口服节拍托泊替康(SKF 104864A)(0.5,1.0和1.5 mg/kg)的日剂量导致微血管密度降低更多(7.5和15 mg /在卵巢癌模型中,但每天用1.5 mg/kg口服托泊替康(SKF 104864A)治疗的小鼠显示食物摄入减少,抗肿瘤作用较小[2]。
• 细胞实验: 将U251，U87，GSCs-U251和GSCs-U87细胞分别以每孔2×104个细胞的密度接种在96孔板中，并孵育24小时。用紫草素和拓扑替康（SKF 104864A）（0.02,0.2,2,20,40μM）给予细胞。处理后，将10μL细胞计数试剂盒-8（CCK-8）加入各孔中，在37℃下再孵育1小时。用酶标仪在450nm处读取光密度（OD）[1]。
• 动物实验: 小鼠[2]对于皮下异种移植研究，我们使用SK-N-BE，SH-SY5Y，KHOS和RH30。将1×10 6个细胞皮下植入每只非肥胖糖尿病/严重联合免疫缺陷（NOD / SCID）小鼠的腹股沟脂肪垫中。当肿瘤直径达到0.5cm时，将动物随机分成4组，每天通过口服强饲法治疗。动物分为：对照组，LDM托泊替康组或LDM TP（1 mg / kg托泊替康），帕唑帕尼组或PZ（150 mg / kg帕唑帕尼）和联合用药组或TP + PZ（1 mg / kg托泊替康（SKF 104864A） ）+ 150 mg / kg Pazopanib）。为了在KHOS骨肉瘤模型中比较脉冲托泊替康与LDM TP，用每周口服剂量的脉冲托泊替康或脉冲TP（15mg / kg拓扑替康）代替PZ。终点的标准是直径超过2.0cm的肿瘤大小或显示出发病迹象的动物。每天测量肿瘤大小直至终点或处死。用卡尺测量长（D）和短直径（d）。肿瘤体积（cm 3）计算为V = 0.5×D×d2。当达到终点或治疗结束时，通过颈椎脱位处死动物。
• 参考文献:

  [1]. Zhang FL, et al. PLoS One. 2013 Nov 26;8(11):e81815.Topoisomerase I inhibitors, Shikonin and Topotecan, inhibit growth and induce apoptosis of glioma cells andglioma stem cells.

  [2]. Kumar S, et al. Metronomic oral topotecan with pazopanib is an active antiangiogenic regimen in mouse models of aggressive pediatric solid tumor. Clin Cancer Res. 2011 Sep 1;17(17):5656-67.

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• 危害码 (欧洲): T: Toxic;
• 风险声明 (欧洲): R25
• 安全声明 (欧洲): 26-36/37/39-45
• 海关编码: 2942000000

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