product name Irinotecan HCl Trihydrate
Description: Irinotecan HCl Trihydrate (also known as CPT-11 HCl Trihydrate) is a semisynthetic derivative of camptothecin with IC50 value of 3.4μM in P388 leukemia. It is developed to avoid toxicity and to improve therapeutic efficacy of camptothecin. It has been approved by FDA for the treatment of patients with metastatic carcinoma of the colon or rectum whose disease has recurred or progressed following 5-fluorouracil-based therapy. Irinotecan is a soluble prodrug of SN-38, it is converted into SN-38 by carboxylesterase enzymes in vivo.
References: Cancer Chemother Pharmacol. 2002 Apr;49(4):329-35; Int J Cancer. 1997 Jan 27;70(3):335-40.
677.18
Formula
C33H38N4O6.HCl.3H2O
CAS No.
136572-09-3
Storage
-20℃ for 3 years in powder form
-80℃ for 2 years in solvent
Solubility (In vitro)
DMSO: 100 mg/mL (147.7 mM)
Water: <1 mg/mL
Ethanol: 7 mg/mL (10.3 mM)
Solubility (In vivo)
30% Propylene glycol, 5% Tween 80, 65% D5W: 30 mg/mL
Synonyms
CPT-11 HCl Trihydrate
other peoduct :
| In Vitro |
In vitro activity: 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. Kinase Assay: Cell Assay: Exponentially growing cells (LoVo and HT-29 cells) are seeded in 20 cm2 Petri dishes with an optimal cell number for each cell line (2 × 104 for LoVo cells, 105 for HT-29 cells). They are treated 2 days later with increasing concentrations of Irinotecan or SN-38 for one cell doubling time (24 hours for LoVo cells, 40 hours for HT-29 cells). After washing with 0.15 M NaCl, the cells are further grown for two doubling times in normal medium, detached from the support with trypsin-EDTA and counted in a hemocytometer. The IC50 values are then estimated as the Irinotecan or SN-38 concentrations responsible for 50% growth inhibition as compared with cells incubated without Irinotecan or SN-38. |
|---|---|
| In Vivo | 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. |
| Animal model | Female nude mice with COLO 320 and WiDr xenografts. |
| Formulation & Dosage | Dissolved in 0.9% NaCl; 20 mg/kg; i.p. injection |
| References | Cancer Chemother Pharmacol. 2002 Apr;49(4):329-35; Int J Cancer. 1997 Jan 27;70(3):335-40. |
