Irinotecan HCl Trihydrate

Catalog No.S2217 Synonyms: CPT-11 HCl Trihydrate

Irinotecan HCl Trihydrate Chemical Structure

Molecular Weight(MW): 677.18

Irinotecan prevents DNA from unwinding by inhibition of topoisomerase 1.

Size Price Stock Quantity  
In DMSO USD 190 In stock
USD 70 In stock
USD 210 In stock
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1 Customer Review

  • Growth inhibitory effects of Irinotecan in human pancreatic cancer cells. Panc1 cells were plated in triplicates into 48-well plates at a density of 10,000 cells/ml. After 24 hours, complete culture medium was changed into fresh low-serum-containing medium (1% FBS) containing DMSO (control) or indicated doses of Irinotecan (Selleckchem). Cell viability 72 hours after treatment was determined by AlamarBlue assay (Invitrogen) according to manufacturer's instructions. Results are expressed as percentages of control, which was arbitrarily assigned 100% viability, and represented as the mean ± standard deviation (SD) of the tripicate wells. 

    Dr. Mikhail Menshikov of Cardiology Research Center. Irinotecan HCl Trihydrate purchased from Selleck.

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Biological Activity

Description Irinotecan prevents DNA from unwinding by inhibition of topoisomerase 1.
Features Irinotecan is a prodrug that is used to treat metastatic colorectal cancer.
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]

Protocol

Cell Research:

[1]

+ Expand
  • 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.


    (Only for Reference)
Animal Research:

[5]

+ Expand
  • Animal Models: Female nude mice with COLO 320 and WiDr xenografts.
  • Formulation: 0.9% NaCl
  • Dosages: 20 mg/kg
  • Administration: Intraperitoneal injection
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 100 mg/mL (147.67 mM)
Ethanol 7 mg/mL (10.33 mM)
Water 1 mg/mL (1.47 mM)
In vivo Add solvents individually and in order:
5% DMSO+saline
20mg/mL

* 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.

Chemical Information

Molecular Weight 677.18
Formula

C33H38N4O6.HCl.3H2O

CAS No. 136572-09-3
Storage powder
in solvent
Synonyms CPT-11 HCl Trihydrate

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Clinical Trial Information

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01928290 Recruiting Stomach Neoplasms|Esophageal Neoplasms Washington University School of Medicine November 8, 2013 Phase 2
NCT01336985 Terminated Neoplasm Metastases|Melanoma|Colorectal Neoplasms National Institutes of Health Clinical Center (CC) March 28, 2011 Phase 1
NCT02316496 Terminated Colorectal Cancer Metastatic Groupe Cooperateur Multidisciplinaire en Oncologie (GERCOR) September 23, 2015 Phase 2
NCT02975882 Not yet recruiting Childhood Solid Neoplasm|Recurrent Central Nervous System Neoplasm|Recurrent Solid Neoplasm|Refractory Central Nervous System Neoplasm Childrens Oncology Group|National Cancer Institute (NCI) September 2017 Phase 1
NCT02967289 Not yet recruiting Colon Cancer (High-risk Stage III; pT4N1 or pT1 to 4 N2) UNICANCER|Canadian Cancer Trials Group January 2017 Phase 3
NCT03009058 Not yet recruiting Metastatic Cancer Immodulon Therapeutics Ltd January 2017 Phase 1|Phase 2

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Topoisomerase Signaling Pathway Map

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID