Irinotecan HCl Trihydrate

Catalog No.S2217 Batch:S221704

Technical Data

Formula	C₃₃H₃₈N₄O₆.HCl.3H₂O
Molecular Weight	677.18	CAS No.	136572-09-3
Solubility (25°C)*	In vitro	DMSO	100 mg/mL (147.67 mM)
		Ethanol	12 mg/mL (17.72 mM)
		Water	1 mg/mL (1.47 mM)
* <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 HCl Trihydrate is a hydrochloride trihydrate of irinotecan (Camptosar, Campto, CPT-11) which is a topoisomerase I inhibitor with IC50 of 15.8 and 5.17 μM for LoVo cells and HT-29 cells, respectively.

Targets

Topo I ^[1]

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 Intraperitoneal injection

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
Intraperitoneal injection

References

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Customer Product Validation

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

: Data from [Data independently produced by , , Biomaterials, 2015, 72:74-89]

: Data from [Data independently produced by , , Mol Cancer Ther, 2018, 17(2):508-520]

: Data from [Data independently produced by , , Carcinogenesis, 2018, 39(1):72-83]

Selleck's Irinotecan HCl Trihydrate has been cited by 87 publications

The novel SMYD3 inhibitor EM127 impairs DNA repair response to chemotherapy-induced DNA damage and reverses cancer chemoresistance [ J Exp Clin Cancer Res, 2024, 43(1):151]	PubMed: 38812026
Establishment, characterization, and biobanking of 36 pancreatic cancer organoids: prediction of metastasis in resectable pancreatic cancer [ Cell Oncol (Dordr), 2024, 10.1007/s13402-024-00939-5]	PubMed: 38619751
Artesunate ameliorates irinotecan-induced intestinal injury by suppressing cellular senescence and significantly enhances anti-tumor activity [ Int Immunopharmacol, 2023, 119:110205]	PubMed: 37104917
Cutoff value of IC50 for drug sensitivity in patient-derived tumor organoids in colorectal cancer [ iScience, 2023, 26(7):107116]	PubMed: 37426352
The role of pregnane X receptor (PXR-in cancer drug resistance and identification of novel PXR antagonists [ Tübingen, 2023, ]	PubMed: None
p53 controls choice between apoptotic and non-apoptotic death following DNA damage [ bioRxiv, 2023, 2023.01.17.524444]	PubMed: 36712034
3D imaging analysis on an organoid-based platform guides personalized treatment in pancreatic ductal adenocarcinoma [ J Clin Invest, 2022, 132(24)e151604]	PubMed: 36282600
Colorectal Cancer Patient-Derived 2D and 3D Models Efficiently Recapitulate Inter- and Intratumoral Heterogeneity [ Adv Sci (Weinh), 2022, e2201539]	PubMed: 35652270
A microfluidic Braille valve platform for on-demand production, combinatorial screening and sorting of chemically distinct droplets [ Nat Protoc, 2022, 10.1038/s41596-022-00740-4]	PubMed: 36261631
Targeting BCL-XL in fibrolamellar hepatocellular carcinoma [ JCI Insight, 2022, 7-17e161820]	PubMed: 36073545

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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