Synonym name: Irinotecan Hydrochloride Trihydrate, 136572-09-3
Catalogue No.: BP0768
Cas No.: 100286-90-6
Formula: C33H39ClN4O6
Mol Weight: 623.147
Botanical Source:
Purity: 95%~99%
Analysis Method: HPLC-DAD or/and HPLC-ELSD
Identification Method: Mass, NMR
Packing: Brown vial or HDPE plastic bottle
Can be supplied from milligrams to grams.
For Reference Standard and R&D, Not for Human Use Directly.
Inquire for bulk scale.
Storage conditions：Short-term storage at 2~8℃, long-term storage at -20 ~ -80℃
Irinotecan Hydrochloride (CAS number: 100286-90-6) is a semi synthetic topoisomerase I inhibitor widely used in clinical research for the treatment of colon and rectal cancer. As an important anti-tumor drug, irinotecan induces cancer cell apoptosis by interfering with DNA replication and transcription processes, significantly improving the survival rate of patients with advanced colorectal cancer. In recent years, with the development of molecular targeted therapy and precision medicine, the mechanism of action of irinotecan hydrochloride and its interactions with various molecular targets have received in-depth attention. This article provides a systematic review of the chemical structure, physicochemical properties, pharmacological activity, mechanism of action, drug evaluation, and clinical application prospects of irinotecan hydrochloride, aiming to provide theoretical basis and research ideas for natural product pharmacology and anti-cancer drug development.
Elinotecan hydrochloride is a water-soluble semi synthetic derivative with the molecular formula C33H38N4O6 · HCl and a molecular weight of 586.6890. Its chemical structure is based on the skeleton of natural product Camptothecin, and water-soluble functional groups are introduced through chemical modification to improve the bioavailability of the drug. The structural characteristics of irinotecan include a pyrrolofuran ring system and an indole ring, forming its unique topoisomerase I inhibitory active center. Its LogP value is 3.4032, indicating moderate lipid solubility, which is beneficial for membrane penetration; The polar surface area (TPSA) is 114.2 Å ², reflecting its moderate polarity, which facilitates the binding of drugs to target proteins. The water solubility of irinotecan hydrochloride is relatively low (0.0621 mg/mL), but its hydrochloride form significantly improves solubility, which is beneficial for clinical administration. The low permeability of the blood-brain barrier suggests limited impact on the central nervous system. The negative result of hERG channel inhibition experiment indicates a low risk of cardiac toxicity. The Ames test result is 0.6, indicating low genotoxicity and good safety.
The parent compound of irinotecan, camptothecin, was initially isolated from Camptotheca acuminata, a plant species distributed in southern China. Camptothecin, as a natural product, has significant anti-tumor activity, but its poor water solubility and high toxicity limit its clinical application. Elinotecan has improved its water solubility and pharmacokinetic properties by introducing hydrophilic groups at the C-10 position of the indole ring through semi synthetic modification of camptothecin. The extraction of camptothecin is usually carried out using organic solvent extraction combined with column chromatography purification technology, while irinotecan is prepared through chemical synthesis process to ensure the purity and inter batch consistency of the drug. In recent years, the development of biosynthetic and metabolic engineering technologies has provided new avenues for the production of camptothecin and its derivatives, particularly in terms of increasing yield and reducing costs.
As a topoisomerase I inhibitor, irinotecan hydrochloride mainly stabilizes the topoisomerase I-DNA complex, blocks the single strand break repair process of DNA, leads to double strand breaks, and subsequently triggers cell cycle arrest and apoptosis. Elinotecan exhibits significant cytotoxicity in various tumor cell lines, particularly with high selectivity and efficacy towards colon and rectal cancer cells. In vivo experiments have shown that irinotecan can significantly inhibit tumor growth and prolong the survival of animal models.
In addition, irinotecan has shown the ability to regulate multiple signaling pathways, including AMPK, STAT3, MAPK1, etc. These signaling molecules play a key role in tumor growth, metastasis, and drug resistance. By regulating BCL2 family proteins, irinotecan promotes apoptosis of tumor cells. Its impact on ABC transporters (such as ABCB1) also helps overcome multidrug resistance and enhance the anti-tumor effect of drugs. The latest research also found that irinotecan may affect the tumor microenvironment and inhibit tumor invasion and metastasis by regulating the expression of inflammatory factors TNF and lipoxygenase ALOX5.
The core mechanism of action of irinotecan hydrochloride is to inhibit topoisomerase I (TOP1), which regulates the supercoiled state of DNA by cleaving and rewiring single strands during DNA replication and transcription. Elinotecan binds to the TOP1-DNA complex, blocking the dissociation step of the enzyme, leading to the accumulation of DNA strand breaks and triggering cell apoptosis signals. This mechanism makes irinotecan highly selective in rapidly proliferating tumor cells.
In addition to TOP1, irinotecan also affects multiple key molecular targets:
AMPK (PRKAA1)As a cellular energy sensor, the activation of AMPK can inhibit the metabolic adaptation of tumor cells. Elinotecan interferes with the energy metabolism of tumor cells by regulating the AMPK signaling pathway.
BCL2 Elinotecan downregulates the expression of anti apoptotic protein BCL2 and promotes mitochondrial mediated cell apoptosis.
STAT3 Elinotecan inhibits the activation of STAT3, blocking its role in tumor cell proliferation and immune escape.
ABCB1 As a multidrug resistance related transporter protein, the expression of ABCB1 affects the intracellular accumulation of drugs, and irinotecan enhances drug sensitivity by inhibiting ABCB1 function.
ALOX5 Lipoxygenase 5 is involved in inflammatory response and tumor microenvironment regulation, and the regulation of its expression by irinotecan helps to inhibit tumor invasiveness.
LCK、MAPK1、GSK3B、TNF These signaling molecules are involved in cell proliferation, differentiation, and inflammatory response, and irinotecan exerts anti-tumor effects through multi-target regulation.
In summary, irinotecan enhances its anti-tumor activity and potential to overcome drug resistance through the synergistic effect of multiple targets and pathways.
The pharmacological evaluation of irinotecan hydrochloride shows that it has good pharmacokinetic characteristics. Although the molecular weight of 586.6890 is relatively large, its moderate lipid solubility (LogP 3.4032) and polar surface area (TPSA 114.2) give it good cell membrane permeability. Although low in water solubility, the hydrochloride form significantly improves solubility and is suitable for intravenous administration. The low permeability of the blood-brain barrier reduces the risk of central nervous system toxicity.
Pharmacokinetic studies have shown that irinotecan is converted into the active metabolite SN-38 by hepatic esterase hydrolysis in vivo, and the latter has much higher anti-tumor activity than the parent drug. SN-38 is metabolized by UDP glucuronosyltransferase (UGT1A1), and UGT1A1 gene polymorphism has a significant impact on drug clearance and toxicity, which is an important basis for personalized medication. Elinotecan and its metabolites are mainly excreted through bile, and patients with liver dysfunction need to adjust the dosage.
In terms of safety, irinotecan does not inhibit hERG channels and has a low risk of cardiac toxicity. The Ames test results showed low genotoxicity, and common adverse reactions in clinical applications include bone marrow suppression and gastrointestinal reactions, but overall tolerability is good.
As one of the core drugs for colorectal cancer chemotherapy, irinotecan hydrochloride has been widely used in clinical practice and combined with other chemotherapy drugs such as fluorouracil and oxaliplatin to form the FOLFIRI regimen, significantly improving the survival rate and quality of life of patients. With the rise of molecular targeted therapy, the combined application of irinotecan with targeted drugs and immune checkpoint inhibitors has become a research hotspot, aiming to overcome drug resistance and enhance efficacy.
Future research directions include:
Individualized medication Dose adjustment based on UGT1A1 genotype to reduce toxic side effects and improve treatment safety.
New drug delivery system Development of delivery systems such as nanocarriers and liposomes to improve drug targeting and bioavailability.
Combination therapy strategy Research on synergistic effects with immunotherapy and targeted therapy to expand the scope of indications.
Research on Drug Resistance Mechanisms In depth analysis of the signaling pathways related to resistance to irinotecan, providing targets for new drug development.
Biological synthesis and green preparation Using synthetic biology techniques to optimize the production process of irinotecan, reduce costs, and increase yield.
In summary, irinotecan hydrochloride plays an irreplaceable role in the treatment of colorectal cancer, and its multi-target mechanism of action and good drug properties provide valuable experience and inspiration for the development of anti-tumor drugs.
As a semi synthetic topoisomerase I inhibitor based on the natural product camptothecin, irinotecan hydrochloride has become an important drug for the treatment of colorectal cancer due to its unique chemical structure and multi-target mechanism of action. Its excellent pharmacological activity and drug properties have enabled it to be widely used in clinical practice and continuously promote the development of anti-tumor therapy. In the future, with the advancement of precision medicine and new drug delivery technologies, irinotecan hydrochloride is expected to have greater potential, improve patient prognosis, and promote innovation and breakthroughs in the field of natural product pharmacology.
