Irinotecan 是喜树碱的衍生物，可抑制拓扑异构酶 I 的作用，可研究结肠癌和直肠癌。它通过与拓扑异构酶 I-DNA 复合物结合来阻止 DNA 链的重新连接，并导致双链 DNA 断裂和细胞死亡。

Irinotecan is an antineoplastic enzyme inhibitor primarily used in the treatment of colorectal cancer. It is a derivative of camptothecin that inhibits the action of topoisomerase I. Irinotecan prevents religation of the DNA strand by binding to topoisomerase I-DNA complex, and causes double-strand DNA breakage and cell death.

单剂量Irinotecan明显增加胃,十二指肠,结肠和肝脏中拓扑异构酶I与DNA的共价结合量.同时,与对照组相比,Irinotecan治疗组的结肠黏膜细胞中DNA链断裂数量明显较高.Irinotecan诱导COLO320异种移植物中92%的最大生长抑制.

Irinotecan在肠道,血浆和肿瘤组织中转化为SN-38。Irinotecan在小细胞肺癌细胞系中的活性明显高于非小细胞肺癌细胞系,而在组织学分型中没有观察到SN-38有明显的差异。Irinotecan被羧酸酯酶活化为SN-38,从而能够与其靶点,拓扑异构酶I相互作用。 Irinotecan的内酯E环和SN-38在水溶液中可逆水解,内酯形式和羧酸盐形式之间的互变取决于PH和温度。Irinotecan主要通过肝脏活化为SN-38。对于相同浓度的Irinotecan和SN-38葡糖苷酸,在肿瘤和正常组织中,β-葡糖醛酸酶介导的SN-38产率均高于Irinotecan形成的SN-38产率。SN-38诱导可裂解复合物浓度依赖性形成,在LoVo细胞和HT-29细胞系中没有明显差异。Irinotecan引起的细胞积聚明显不同,在HT-29细胞中的水平始终高于LoVo细胞。

Irinotecan is dissolved in DMSO and stored, and then diluted with appropriate medium before use[1]. To determine the effects of Irinotecan in combination with 5-FU, the MTT assay is used. Depending on the cell lines, 10,000 to 20,000 cells per well are seeded in 96-well plates and incubated for 24 h in complete medium. On day 2, cells are incubated in the absence or presence of Irinotecan for 30 min followed by 5-FU for 24 h. After another 24 h in complete medium without any additives, MTT reagent is added on day 4 to initiate the assay and the cells are incubated for an additional 4 h at 37°C. After removal of the medium and dissolving the crystals with acidified isopropanol, the samples are analyzed using an ELISA plate reader at 570 nm. The value at 650 nm is subtracted as background[1].

97682-44-5

C33H38N4O6

586.689

(+)-Irinotecan;CPT-11;伊立替康;Topotecin

DMSO:32 mg/mL (54.5 mM),Need ultrasonic
Powder: -20°C for 3 years
In solvent: -80°C for 2 years