Irinotecan hydrochloride
[CAS# 100286-90-6]

Identification

• Classification: Biochemical >> Plant extracts
• Name: Irinotecan hydrochloride
• Synonyms: (S)-[1,4'-Bipiperidine]-1'-carboxylic acid, 4,11-diethyl-3,4,12,14-tetrahydro-4-hydroxy-3,14-dioxo-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl ester hydrochloride
• Molecular Formula: C₃₃H₃₈N₄O₆.HCl
• Molecular Weight: 623.15
• CAS Registry Number: 100286-90-6
• EC Number: 600-054-0
• SMILES: CCC1=C2CN3C(=CC4=C(C3=O)COC(=O)[C@@]4(CC)O)C2=NC5=C1C=C(C=C5)OC(=O)N6CCC(CC6)N7CCCCC7.Cl

Properties

• Melting point: 250-256 °C (dec.)

Safety Data

• Hazard Symbols: GHS07 Warning
• Risk Statements: H302
• Safety Statements: P264-P270-P301+P317-P330-P501

Hazard Classification

Hazard	Class	Category Code	Hazard Statement
Acute toxicity	Acute Tox.	4	H302

Discovery and Applications

Irinotecan hydrochloride, a prominent chemotherapeutic agent, was discovered in the early 1980s. Its origins trace back to the research into natural products derived from the Camptotheca acuminata tree, native to China, which had been used in traditional medicine for its anticancer properties. The active compound, camptothecin, was isolated from this tree in the 1960s, but its clinical use was limited due to severe toxicity and poor solubility. Efforts to modify camptothecin led to the development of irinotecan hydrochloride, a semi-synthetic derivative that showed improved pharmacological properties. It was first synthesized by Japanese researchers and later underwent extensive clinical trials, demonstrating significant efficacy in treating various cancers, particularly colorectal cancer. The FDA approved irinotecan hydrochloride in 1996, marking a milestone in cancer treatment.

Irinotecan hydrochloride is primarily used as a chemotherapeutic agent in the treatment of colorectal cancer, often in combination with other drugs. Its mechanism of action involves inhibiting topoisomerase I, an enzyme crucial for DNA replication. By stabilizing the complex between topoisomerase I and DNA, irinotecan induces DNA damage during replication, leading to cell death. This action makes it particularly effective against rapidly dividing cancer cells.

One of the main applications of irinotecan is in the first-line treatment of metastatic colorectal cancer, often combined with other chemotherapeutic agents like 5-fluorouracil and leucovorin in a regimen known as FOLFIRI. This combination has been shown to improve survival rates and quality of life in patients with advanced-stage colorectal cancer. Irinotecan is also used in the second-line treatment for patients who have not responded to initial therapies.

Beyond colorectal cancer, irinotecan has shown efficacy in treating other types of cancer, including small cell lung cancer, gastric cancer, and ovarian cancer. Its versatility is due to its potent mechanism of action and ability to be combined with other chemotherapy drugs to enhance therapeutic effects.

In recent years, research has focused on optimizing irinotecan's delivery and reducing its side effects. Liposomal formulations, which encapsulate the drug in lipid-based vesicles, have been developed to improve its pharmacokinetic profile and minimize toxicities. Additionally, pharmacogenetic testing can help identify patients who may be at higher risk of severe side effects due to genetic variations in the enzymes that metabolize irinotecan, allowing for personalized dosing strategies.

References

2000. Differential activity of topotecan, irinotecan and SN-38 in fresh human tumour cells but not in cell lines. European Journal of Cancer, 36(16).
DOI: 10.1016/s0959-8049(00)00289-6

2003. The emerging role of irinotecan (CPT-11) in the treatment of malignant glioma in brain tumors. Cancer, 97(8).
DOI: 10.1002/cncr.11305

2003. Prevention of irinotecan plus 5-fluorouracil/leucovorin-induced diarrhoea by oral administration of neomycin plus bacitracin in first-line treatment of advanced colorectal cancer. Annals of Oncology, 14(5).
DOI: 10.1093/annonc/mdg193