(4S)-4-乙基-4-羟基-11-(2-三甲基硅基)乙基)-1H-吡喃并[3,4:6,7]氮茚并[1,2-B]喹啉-3

中文名称:

(4S)-4-乙基-4-羟基-11-(2-三甲基硅基)乙基)-1H-吡喃并[3,4:6,7]氮茚并[1,2-B]喹啉-3,14(4H,12H)-二酮

中文同义词:

(4S)-4-乙基-4-羟基-11-(2-三甲基硅基)乙基)-1H-吡喃并[3,4:6,7]中氮茚并[1,2-B]喹啉-3,14(4H,12H)-二酮;(4S)-4-乙基-4-羟基-11-(2-三甲基硅基)乙基)-1H-吡喃并[3,4:6,7]氮茚并[1,2-B]喹啉-3,14(4H,12H)-二酮

英文名称:

Karenitecin

英文同义词:

Karenitecin;(4S)-4-Ethyl-4-hydroxy-11-(2-trimethylsilyl)ethyl)-1H-pyrano[3,4:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione;BNP 1350;Cositecan;DB 172;MCC 12824;1H-Pyrano[3,4:6,7]indolizino[1,2-b]quinoline-3,14(4H,12H)-dione, 4-ethyl-4-hydroxy-11-[2-(trimethylsilyl)ethyl]-, (4S)-

CAS号:

203923-89-1

分子式:

C25H28N2O4Si

分子量:

448.59

EINECS号:

相关类别:

植物提取物;药品试剂-试剂;标准品 -中药标准品

Mol文件:

203923-89-1.mol

沸点 

727.2±60.0 °C(Predicted)

密度 

1.29±0.1 g/cm3(Predicted)

酸度系数(pKa)

11.27±0.20(Predicted)

生物活性

Karenitecin (Cositecan) 是拓扑异构酶 I (topoisomerase I) 抑制剂，具有高效的抗肿瘤活性。

靶点

Topoisomerase I

Topoisomerase I

体外研究

Karenitecin is a topoisomerase I inhibitor, with potent anti-cancer activity. Karenitecin inhibits cell growth of A253 cells with IC 10 , IC 50 , and IC 90 values of 0.01, 0.07, and 0.7 μM after 2 h treatment. Karenitecin induces DNA damage (0.01, 0.07, and 0.7 μM), and increases cyclin E and cdk2 protein expression in A253 cells (0.07, and 0.7 μM). Karenitecin markedly enhances the cyclin B/cdc2-associated kinase activity at low concentration, but slightly suppresses this kinase activity at higher concentration. Karenitecin inhibits several human colon cancer cell lines such as COLO205, COLO320, LS174T, SW1398 and WiDr cells, with IC 50 s of 2.4 nM, 1.5 nM, 1.6 nM, 2.9 nM, and 3.2 nM, respectively.

体内研究

Karenitecin shows maximum growth inhibition of 61% on COLO320 cells and 54% on COLO205 colon cancer cells via i.p. administration of 1 mg/kg in mice. Karenitecin (1.0 mg/kg daily × 5 i.p.) significantly suppresses growth inhibition both in the parental Pgp-negative xenografts and in the Pgp-positive xenografts.