Irinotecan HCl

SKU: orb1310567

Description

Irinotecan hydrochloride trihydrate (CPT-11 HCl Trihydrate) is a topoisomerase I inhibitor that stabilizes the DNA-enzyme complex, preventing DNA religation and causing lethal double-strand breaks. It is widely used in cancer research for studying chemotherapy mechanisms and efficacy in both cellular and animal models.

Research Area

Cell Biology

Key Properties

• CAS Number: 136572-09-3
• MW: 586.69 ∙ 36.46 ∙ 54.05
• Purity: >98%
• Formula: C₃₃H₃₈N₄O₆ ∙ HCl ∙ 3H₂₀
• SMILES: O.O.O.Cl.CCc1c2Cn3c(cc4c(COC(=O)[C@]4(O)CC)c3=O)-c2nc2ccc(OC(=O)N3CCC(CC3)N3CCCCC3)cc12
• Target: Topoisomerase
• Solubility: Soluble in DMSO (up to 50 mg/ml), in Water (up to 4 mg/ml) or in Ethanol (up to 4 mg/ml).

Bioactivity

• In Vivo:
  In LoVo and HT-29 cell lines, Irinotecan induces a similar number of cleavable complexes at IC50 concentrations, with no significant difference observed between the two. The formation of cleavable complexes by SN-38 is concentration-dependent and consistent across both cell lines. Notably, intracellular accumulation of Irinotecan differs significantly, with consistently higher levels in HT-29 cells compared to LoVo cells. Carboxylesterase activation of Irinotecan to SN-38 (primarily in the liver) facilitates interaction with its target, topoisomerase I, in plasma, intestines, and tumor tissues. The hydrolysis of Irinotecan’s lactone E-ring and SN-38 is reversible in aqueous solution, with the interconversion of their carboxylate and lactone forms dependent on temperature and pH. For the same concentration of SN-38 glucuronide and Irinotecan in tumor and normal tissues, the yield of SN-38 via β-glucuronidase mediation exceeds that of SN-38 produced from Irinotecan. In SCLC cell lines, Irinotecan exhibits markedly greater activity than in NSCLC cell lines, while tissue histology does not reveal significant differences in SN-38 efficacy.
• In Vitro:
  In the liver, stomach, duodenum, and colon, a single dose of Irinotecan significantly increases the covalent binding of topoisomerase I to DNA. Compared to the control group, there is a marked increase in DNA strand breaks within the colonic mucosal cells in the Irinotecan-treated group. In COLO320 xenografts, Irinotecan induces a 92% maximum growth inhibition.
• Cell Research:
  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. (Only for Reference)

Storage & Handling

• Storage: -20°C
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

Topo I, Topoisomerase, Autophagy, (+)-Irinotecan hydrochloride, CPT-11 hydrochloride, CPT-11 HCl, CPT-11 HCl Trihydrate, inhibit, Irinotecan HCl, Irinotecan HCl Trihydrate, Irinotecan hydrochloride, Irinotecan Hydrochloride, Irinotecan hydrochloride trihydrate, Irinotecan hydrochloride Trihydrate, Inhibitor

Compound Identifiers

PubChem CID

60837