irinotecan hydrochloride

Overview

Irinotecan hydrochloride (CPT-11) is a semisynthetic derivative of camptothecin and a potent inhibitor of Topoisomerase I (Topo I), the enzyme responsible for relieving torsional stress in DNA during replication and transcription. By stabilizing the covalent Topo I–DNA cleavage complex, irinotecan prevents re-ligation of single-strand DNA breaks, ultimately causing irreversible double-strand breaks and apoptosis in rapidly dividing cells. The drug is a prodrug that requires carboxylesterase-mediated conversion to its active metabolite, SN-38, which carries the majority of its cytotoxic activity. Hepatic and intestinal uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1) further conjugates SN-38 to an inactive glucuronide (SN-38G), a step critical for both detoxification and the pathogenesis of delayed-onset diarrhea—one of its most clinically significant adverse effects.

Irinotecan is approved and widely used as a first- and second-line chemotherapeutic agent, most prominently in advanced and metastatic colorectal cancer (CRC), where it forms the backbone of regimens such as FOLFIRI (fluorouracil, folinic acid, and irinotecan) and FOLFIRINOX (combined with oxaliplatin and gemcitabine in pancreatic cancer contexts). Its clinical utility extends to gastric carcinoma, neuroblastoma, and other solid tumors, often in combination with targeted agents such as cetuximab and bevacizumab, or with cytotoxic partners such as temozolomide and oxaliplatin.

Focus of Latest Publications

Recent publications on irinotecan hydrochloride have focused on improving its therapeutic performance, predicting response, and mitigating toxicity, particularly in colorectal cancer and other solid tumors. Several studies examined irinotecan in combination with delivery systems or adjunct agents designed to enhance efficacy and tolerability. A multistage formulation co-delivering irinotecan hydrochloride with bevacizumab in zein nanoparticles embedded in a thermo-sensitive hydrogel showed sustained release, improved permeability across a 3D intestinal barrier, and cytotoxic activity in colorectal cancer monolayers and spheroids. In another colorectal cancer study, a self-assembled nanomedicine incorporating irinotecan and indole-3-carbinol was reported to increase irinotecan uptake, promote endoplasmic reticulum stress, and improve antitumor activity while counteracting irinotecan-induced steatohepatitis-associated liver metastasis.

Other recent work has addressed biomarkers and mechanisms relevant to irinotecan-based therapy. In pancreatic ductal adenocarcinoma, a ratiometric fluorescent sensor for carboxylesterase 2 activity was shown to correlate strongly with response to irinotecan (CPT-11)-based regimens, including FOLFIRINOX, supporting its potential use for predicting treatment sensitivity before therapy. In colorectal cancer cell lines, irinotecan induced both genotoxic damage and reactive oxygen species production in a dose-dependent manner, with similar effects observed in TP53 wild-type and TP53-null HCT116 cells under the tested non-cytotoxic conditions. These findings suggest a drug-specific oxidative and DNA-damaging profile that may be relevant for combination strategies.

Irinotecan hydrochloride also appeared in studies of local delivery and disease-specific treatment regimens. A sodium alginate sulfate microsphere platform achieved high loading capacity for irinotecan hydrochloride and was proposed as a stabilized embolic system for transarterial chemoembolization, with sustained release and favorable embolization stability in a pig renal artery model. In relapsed or refractory neuroblastoma, the bevacizumab/irinotecan/temozolomide (BIT) regimen was highlighted as a guideline-supported option based on prior clinical evidence. In colorectal cancer, combining irinotecan with FASN inhibition was reported to synergistically reduce xenograft growth and delay tumor relapse, with further potentiation by olaparib maintenance treatment.

Across these publications, irinotecan hydrochloride was consistently studied as part of efforts to improve delivery, personalize treatment, or overcome limitations such as toxicity, resistance, and relapse. The overall theme is that irinotecan remains a clinically important topoisomerase I-targeting therapy, but its recent research emphasis has shifted toward formulation engineering, biomarker-guided selection, and rational combinations that enhance antitumor efficacy while reducing adverse effects.

Key Publications

• NEWJun Reprogramming Aromatic Camptothecins into TOP1 Degraders via Synergistic Hydrophobic Tagging and Supramolecular Assembly. (Journal of the American Chemical Society, 2026, PMID 42378337): "Our lead candidate, SN-38-A2, demonstrates potent TOP1 degradation and achieves superior tumor regression in xenograft models compared to clinical irinotecan."
• May Ratiometric Fluorescent Chemosensing for Predicting Response to Irinotecan-Based Therapies in Pancreatic Ductal Adenocarcinoma. (ACS sensors, 2026, PMID 42043185): "...an enzyme responsible for metabolically activating irinotecan (CPT-11), a component of FOLFIRINOX..."
• May A Self-Assembled Irinotecan Nanomedicine Abrogates Steatohepatitis-Induced Liver Metastasis and Potentiates Antitumor Efficacy against Colorectal Cancer. (ACS nano, 2026, PMID 42007878): "Irinotecan is a widely used chemotherapeutic agent for the treatment of advanced and metastatic colorectal cancer (CRC)."
• Apr Development and in vitro cytotoxic profiles of multistage systems containing irinotecan hydrochloride and bevacizumab for the treatment of human colorectal carcinoma. (International journal of pharmaceutics, 2026, PMID 41881271): "...for the co-delivery of bevacizumab (BVZ) and irinotecan (Iri)."
• Jun Induction of genotoxic damage and ROS production in HCT116 TP53+/+ and HCT116TP53-/- colorectal cancer cell lines by anticancer drugs. (Mutagenesis, 2026, PMID 41870588): "...after exposure to four commonly used anticancer agents: oxaliplatin (OXA), irinotecan (IRI), paclitaxel (PAC), and 5-fluorouracil (5-FU)."
• May The Efficacy and Safety of Bevacizumab/Irinotecan/Temozolomide (BIT) for Relapsed/Refractory Neuroblastoma: The UK Children's Cancer and Leukaemia Group Experience. (Pediatric blood & cancer, 2026, PMID 41840813): "Based on data from the BEACON trial, since 2021 the UK national guidelines recommend bevacizumab, irinotecan, and temozolomide (BIT) for patients with relapsed/refractory disease."
• May Self-expanding sodium alginate sulfate drug-loaded microspheres for stabilized arterial embolization. (Carbohydrate polymers, 2026, PMID 41832022): "high loading capacity (68.0 mg/g, Irinotecan hydrochloride)"
• May Rational design, synthesis and effective mechanism of sophoridine and matrine contains 2,3,4-triphenylpyridine derivatives as TopoⅠ inhibitors for the treatment of gastric carcinoma. (European journal of medicinal chemistry, 2026, PMID 41812411): "In vivo studies demonstrated that the tumor growth inhibition (TGI) rates for sophoridine, matrine, H4, K8, and irinotecan were 19.3%, 9.7%, 45.3%, 36.6%, and 87.0%, respectively."
• Jun Design, synthesis, and biological evaluation of a hydrophilic 20-O-glycyl ester prodrug of 10-methoxycamptothecin against lung cancer. (Bioorganic chemistry, 2026, PMID 41812429): "Although its potency was modestly reduced compared with that of MCPT, MG16 was substantially more active than SN-38, the active metabolite of CPT-11."
• May Xiao-Chaihu-Tang preserves intestinal barrier and ameliorates irinotecan-evoked delayed diarrhea by anchoring endogenous tryptophol to modulate inflammation and oxidation dependent on AhR-UGT1A1-microbiota axis. (Journal of ethnopharmacology, 2026, PMID 41713817): "It also exhibits promising efficacy against chemotherapy irinotecan (CPT-11)-induced delayed diarrhea (DD)."