The Sound of Evolution
Irinotecan
Mechanism of action:
Irinotecan is a camptothecin derivative. After entering the body, it is metabolized by carboxylesterase into SN-38. SN-38 inhibits the activity of DNA topoisomerase I. Under normal conditions, topoisomerase I temporarily cuts single-stranded DNA during DNA replication to relieve torsional stress and then religates it. SN-38 stabilizes the DNA-topoisomerase I cleavage complex, preventing the broken DNA strand from being rejoined, thereby inducing DNA damage and apoptosis.
Reference(s):
1. Ramesh M et al. (2010). Irinotecan and its active metabolite, SN-38: review of bioanalytical methods and recent update from clinical pharmacology perspectives. Biomed Chromatogr.
2. Chabot GG et al. (1997). Clinical pharmacokinetics of irinotecan. Clin Pharmacokinet.
3. Rothenberg ML et al. (2001). Irinotecan (CPT-11): recent developments and future directions—colorectal cancer and beyond. Oncologist.