基本信息

产品描述

Irinotecan HCl Trihydrate通过抑制Topoisomerase 1（拓扑异构酶1）而防止DNA解链。

靶点（IC50 & Targe）

Topo I

体外研究

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。IC50浓度下的Irinotecan在LoVo细胞和HT-29细胞系中诱导相似量的可裂解复合物。SN-38诱导可裂解复合物浓度依赖性形成，这在LoVo细胞和HT-29细胞系中没有明显差异。Irinotecan引起的细胞积聚显著不同，在HT-29细胞中的水平始终高于LoVo细胞。[1] 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。[2] Irinotecan在肠道，血浆和肿瘤组织中转化为SN-38。[3] Irinotecan在SCLC细胞系中的活性显著高于NSCLC细胞系，而在组织学分型中没有观察到SN-38有明显的差异。[4]

体内研究

在COLO320异种移植物中，Irinotecan诱导92%的最大生长抑制。[5]单剂量Irinotecan显著增加胃，十二指肠，结肠和肝脏中拓扑异构酶I与DNA的共价结合数量。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。[6]

细胞实验

Cell lines: LoVo 和HT-29 细胞

Concentrations: 0 μM -100 μM

Incubation Time: 48小时

Method:指数生长的细胞(LoVo和HT-29细胞)以每种细胞系的最佳接种数量(LoVo 细胞2×10⁴；HT-29细胞10⁵)接种于20 cm² Petri培养皿。2天后，用逐渐增加浓度的Irinotecan或SN-38处理一个细胞倍增时间(LoVo 细胞24小时，HT-29细胞40 小时)。0.15 M NaCl洗涤后，细胞进一步在正常培养基中生长两个倍增时间，从胰蛋白酶-EDTA的支撑物中分离，并在血细胞计数器上计数。IC50值的估算如下：与不含Irinotecan 或SN-38培养的细胞相比，引起50%生长抑制的Irinotecan 或SN-38浓度。

(Only for Reference)

动物实验

Animal Models: 负荷COLO 320和WiDr异种移植物的雌性裸鼠

Formulation: 0.9% NaCl

Dosages: 20 mg/kg

Administration: 腹腔注射

(Only for Reference)

参考文献

[1] Pavillard V, et al. Cancer Chemother Pharmacol. 2002, 49(4), 329-335.

[2] Tobin P, et al. Br J Clin Pharmacol. 2006, 62(1), 122-129.

[3] Shingyoji M, et al. Cancer Sci. 2004, 95(6), 537-540.

[4] van Ark-Otte J, et al. Br J Cancer. 1998, 77(12), 2171-2176.

[5] Jansen WJ, et al. Int J Cancer. 1997, 70(3):335-340.

[6] Na YS, et al. Cancer Chemother Pharmacol. 2011, 68(2), 389-398.

[7] Wagner LM, et al. Pediatr Blood Cancer. 2007, 48(2), 132-139

安全信息

图形或危害标志
提示语	Danger
危险说明	H302 H372
防范说明	P260 P270 P301+P312 P330 P314 P501
RTECS	DW1060750

基本信息

安全信息

图形或危害标志
危险性说明	H302: Harmful if swallowed. H315: Causes skin irritation. H319: Causes serious eye irritation. H335: May cause respiratory irritation. H372: Causes damage to organs Blood. Digestive tract..
防范说明	P233: Keep container tightly closed. P260: Do not breathe . P261: Avoid breathing P264: Wash hands thoroughly after handling. P270: Do not eat, drink or smoke when using this product. P271: Use only outdoors or in a well-ventilated area. P280: Wear . P301 + P312: IF SWALLOWED: Call a POISON CENTER or doctor/physician if you feel unwell. P302 + P352: IF ON SKIN: Wash with plenty of soap and water. P304: IF INHALED: . P304 + P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P305 + P351 + P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continue rinsing. P312: Call a POISON CENTER or doctor/physician if you feel unwell. P314: Get medical advice/attention if you feel unwell. P321: Specific treatment (see . on this label). P330: Rinse mouth. P332 + P313: If skin irritation occurs: Get medical advice/ attention. P337 + P313: If eye irritation persists: Get medical advice/attention. P340: Remove victim to fresh air and keep at rest in a position comfortable for breathing. P362: Take off contaminated clothing and wash before reuse. P403: Store in a well-ventilated place. P403 + P233: Store in a well-ventilated place. Keep container tightly closed. P405: Store locked up. P501: Dispose of contents/container to local regulations.