For research use only. Not Intended for Therapeutic Use!
|Molecular Formula:||C₃₃H₃₈N₄O₆. HCl|
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Irinotecan Hcl(CPT-11 Hcl) prevents DNA from unwinding by inhibition of topoisomerase 1.
Irinotecan is activated to SN-38 by carboxylesterases to become able to interact with its target, topoisomerase I. Irinotecan induces similar amounts of cleavable complexes at its IC50 in LoVo cells and HT-29 cell lines. SN-38 induces a concentration-dependent formation of cleavable complexes, which is not significantly different in LoVo cells and HT-29 cell lines. Cell accumulation of Irinotecan is markedly different, reaching consistently higher levels in HT-29 cells than in LoVo cells. The lactone E-ring of Irinotecan and SN-38 hydrolyses reversibly in aqueous solutions, and the interconversion between the lactone and carboxylate forms is dependent on pH and temperature. Liver is primarily responsible for the activation of Irinotecan to SN-38. At equal concentrations of Irinotecan and SN-38 glucuronide, the rate of beta-glucuronidase-mediated SN-38 production is higher than that formed from Irinotecan in both tumour and normal tissue. Irinotecan is also converted to SN-38 in intestines, plasma and tumor tissues. Irinotecan is significantly more active in SCLC than in NSCLC cell lines, whereas no significant difference between histological types is observed with SN-38. In COLO 320 xenografts, Irinotecan induces a maximum growth inhibition of 92%. A single dose of Irinotecan significantly increases amounts of topoisomerase I covalently bound to DNA in stomach, duodenum, colon and liver. Concomitantly, the Irinotecan-treated group shows significantly higher amounts of DNA strand breaks in colon mucosa cells compared to the control group.,
. Roy AC, Park SR, Cunningham D, et al. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Feb 13
. JY Douillard, D Cunningham, AD Roth, M Navarro, et al. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. The Lancet, 2000, 355( 9209): 1041 - 1047.
. Prof Philippe Rougier, Eric Van Cutsem, Emilio Bajetta, et al. Randomised trial of irinotecan versus fluorouracil by continuous infusion after fluorouracil failure in patients with metastatic colorectal cancer. The Lancet, 1998, 352 ( 9138): 1407 - 1412.
. Armand JP, Ducreux M, Mahjoubi M et al. CPT-11 (irinotecan) in the treatment of colorectal cancer. Eur J Cancer. 1995 Jul-Aug;31A(7-8):1283-7.