TAS-103 dihydrochloride 是可用于癌症研究的一种 DNA 拓扑异构酶 I/II 双重抑制剂。

TAS-103 (dihydrochloride) is a novel anticancer agent targeting both topoisomerase (Topo) I and Topo II.

The in vitro antitumor effects of TAS-103 were compared with those of other known Topo I and Topo II inhibitors. TAS-103 inhibited DNA synthesis more strongly than RNA and protein synthesis, and induced an increase of cell population in the S-G2/M phase. The cytotoxicity of TAS-103 was strongest against S-phase cells, but its cell cycle phase specificity was not clear, and depended on drug concentration and exposure time. The cytotoxicity of TAS-103 (IC50: 0.0030-0.23 microM) against various tumor cell lines was much stronger than that of VP-16 and comparable to that of SN-38. The cytotoxicity of TAS-103 seemed to be more related to the amount of protein-DNA complexes than to the accumulation of TAS-103 in the cells. P-Glycoprotein (P-gp)-mediated MDR, CDDP-resistant and 5-FU-resistant cell lines did not show cross-resistance to TAS-103. Although PC-7/CPT cells bearing a Topo I gene mutation showed cross-resistance to TAS-103, the sensitivity of P388/CPT, HT-29/CPT and St-4/CPT cells, showing decreased Topo I expression, was not changed. KB/VM4 and HT-29/Etp cells, showing decreased Topo II expression, were slightly cross-resistant to TAS-103. These results suggest that TAS-103 may act as an inhibitor of both Topo I and Topo II at the cellular level[1].

174634-09-4

C20H21Cl2N3O2

406.31

6-[[2-(二甲基氨基)乙基]氨基]-3-羟基-7H-茚并[2,1-C]喹啉-7-酮二盐酸盐;BMS-247615 dihydrochloride;TAS-103 (dihydrochloride)

H2O:50 mg/mL (123.06 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years