盐酸拓扑替康

熔点 213-218°C
存贮条件 2-8°C储存
描述
别名 盐酸拓扑特康;TPT (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　
生化机理
Description:
IC50 Value: 37-280 uM (Human glioma cell lines) [1]
Topotecan (TPT, 9-dimethylaminomethyl-10-hydroxycamptothecin) is the first topoisomerase I-directed cytotoxic agent to enter clinical trials in the United States.
in vitro: Human glioma cell lines (U87, U138 and U373) displayed different sensitivities to topotecan (IC50range: 0.037 microM to 0.280 microM) in cell culture [1]. Examination of the IC50 values observed in colony-forming assays revealed that the CHRC5 cells were 15-fold (SD, +/- 3; n = 3) resistant to TPT after a 1-h exposure and 3.2-fold (SD, +/- 1.4; n = 4) resistant in continuous exposure experiments[2]. The DNA histograms at 4, 24, 48 and 72 h indicate that topotecan at IC80 concentrations causes accumulation of cells in S and G2/M phases, whereas gemcitabine at IC80 concentrations causes, accumulation of cells in G1 phase. Both compounds induced p53 and p21 expression in the H460 cell line but not in the H322 cell line [3]
in vivo: Combination oftopotecan + pazopanib (TP + PZ) showed significant antitumor activity and significant enhancement in survival compared with the respective single agents in all models [4].
Clinical trial: Phase II Study of Topotecan and Bevacizumab in Advanced, Refractory Non-small-cell Lung Cancer.