Irinotecan

Catalog No.S1198 Batch:S119811

Technical Data

Formula	C₃₃H₃₈N₄O₆
Molecular Weight	586.68	CAS No.	97682-44-5
Solubility (25°C)*	In vitro	DMSO	25 mg/mL (42.61 mM)
		Water	Insoluble
		Ethanol	Insoluble
* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description

Irinotecan is a topoisomerase I inhibitor for LoVo cells and HT-29 cells with IC50 of 15.8 μM and 5.17 μM, respectively.

Targets

Topo I ^[1]
(LoVo, HT-29 cells)

In vitro

Irinotecan is activated to SN-38 by carboxylesterases to become able to interact with its target, topoisomerase I. Irinotecan induces similar amounts of cleavable complexes at its IC50 in LoVo cells and HT-29 cell lines. SN-38 induces a concentration-dependent formation of cleavable complexes, which is not significantly different in LoVo cells and HT-29 cell lines. Cell accumulation of Irinotecan is markedly different, reaching consistently higher levels in HT-29 cells than in LoVo cells. ^[1] The lactone E-ring of Irinotecan and SN-38 hydrolyses reversibly in aqueous solutions, and the interconversion between the lactone and carboxylate forms is dependent on pH and temperature. Liver is primarily responsible for the activation of Irinotecan to SN-38. At equal concentrations of Irinotecan and SN-38 glucuronide, the rate of beta-glucuronidase-mediated SN-38 production is higher than that formed from Irinotecan in both tumour and normal tissue. ^[2] Irinotecan is also converted to SN-38 in intestines, plasma and tumor tissues. ^[3] Irinotecan is significantly more active in SCLC than in NSCLC cell lines, whereas no significant difference between histological types is observed with SN-38. ^[4]

In vivo

In COLO 320 xenografts, Irinotecan induces a maximum growth inhibition of 92%. ^[5] A single dose of Irinotecan significantly increases amounts of topoisomerase I covalently bound to DNA in stomach, duodenum, colon and liver. Concomitantly, the Irinotecan-treated group shows significantly higher amounts of DNA strand breaks in colon mucosa cells compared to the control group. ^[6]

Features

Irinotecan is a prodrug that is used to treat metastatic colorectal cancer.

Protocol (from reference)

Cell Assay:^{^[1]}	Cell lines LoVo and HT-29 cells Concentrations 0 μM -100 μM Incubation Time 48 hours Method 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.
Animal Study:^{^[5]}	Animal Models Female nude mice with COLO 320 and WiDr xenografts Dosages 20 mg/kg Administration Administered via i.p.

Cell Assay:^{^[1]}

Cell lines
LoVo and HT-29 cells
Concentrations
0 μM -100 μM
Incubation Time
48 hours
Method
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.

Animal Study:^{^[5]}

Animal Models
Female nude mice with COLO 320 and WiDr xenografts
Dosages
20 mg/kg
Administration
Administered via i.p.

References

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Customer Product Validation

: , , Biomaterials, 2015, 72:74-89.

: Data independently produced by Dr. Edita Aksamitiene from Thomas Jefferson University, , Dr. Mikhail Menshikov of Cardiology Research Center

Selleck's Irinotecan has been cited by 43 publications

AMG 193, a Clinical Stage MTA-Cooperative PRMT5 Inhibitor, Drives Antitumor Activity Preclinically and in Patients With MTAP-Deleted Cancers [ Cancer Discov, 2024, 10.1158/2159-8290.CD-24-0887]	PubMed: 39282709
Transgelin-2, a novel cancer stem cell-related biomarker, is a diagnostic and therapeutic target for biliary tract cancer [ BMC Cancer, 2024, 24(1):357]	PubMed: 38509504
Visualization strategies to aid interpretation of high-dimensional genotoxicity data [ Environ Mol Mutagen, 2024, 10.1002/em.22604]	PubMed: 38757760
In-situ cryo-immune engineering of tumor microenvironment with cold-responsive nanotechnology for cancer immunotherapy [ Nat Commun, 2023, 14(1):392]	PubMed: 36693842
Metabolic classification suggests the GLUT1/ALDOB/G6PD axis as a therapeutic target in chemotherapy-resistant pancreatic cancer [ Cell Rep Med, 2023, 4(9):101162]	PubMed: 37597521
Metabolic classification suggests the GLUT1/ALDOB/G6PD axis as a therapeutic target in chemotherapy-resistant pancreatic cancer [ Cell Rep Med, 2023, S2666-3791(23)00315-4]	PubMed: 37597521
Thioparib inhibits homologous recombination repair, activates the type I IFN response, and overcomes olaparib resistance [ EMBO Mol Med, 2023, e16235.]	PubMed: 36652375
TPX2 enhances the transcription factor activation of PXR and enhances the resistance of hepatocellular carcinoma cells to antitumor drugs [ Cell Death Dis, 2023, 14(1):64]	PubMed: 36707511
Spatial and clonality-resolved 3D cancer genome alterations reveal enhancer-hijacking as a potential prognostic marker for colorectal cancer [ Cell Rep, 2023, 42(7):112778]	PubMed: 37453058
Genetic assessment of pathogenic germline alterations in lysosomal genes among Asian patients with pancreatic ductal adenocarcinoma [ J Transl Med, 2023, 21(1):730]	PubMed: 37848935

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