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Irinotecan

Catalog No.
A5133
Topoisomerase I inhibitor
Grouped product items
SizePriceStock Qty
10mM (in 1mL DMSO)
$55.00
In stock
100mg
$50.00
In stock

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Email: [email protected]

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Background

Irinotecan (CPT-11), a prodrug for treating metastatic colorectal cancer, is a topoisomerase I inhibitor for LoVo cells and HT-29 cells with IC50 of 15.8 μM and 5.17 μM, respectively [1].In vivo, Irinotecan is converted to SN-38, its most active metabolite, by carboxylesterase converting enzyme (CCE) [2].

In vitro: Irinotecan induced similar amounts of cleavable complexes in LoVocells and HT-29 cell lines with the IC50 of 15.8 μM and 5.17 μM, respectively [1].After addition of 157 mM irinotecan to plasma, SN-38 concentration showed linear increase during the first 60-min period, followed by a plateau.In the first 60 min, mean and standard deviation of the conversion rate were 515.9 ± 50.1 pmol/ml/h (n = 69), with a coefficient of variation of 0.097 [2]. Irinotecan (CPT-11) was significantly more active in SCLC than in NSCLCcelllines (P = 0.0036). CE activity appeared to be associated with higher sensitivity to CPT-11 in human lung cancercelllines and may partly explain the difference in the in vitro sensitivity to CPT-11 between SCLC and NSCLCcells [3].In vitro, the sensitivity to CPT-11 and SN-38 was highest in LS174T and COLO 320cells, intermediate in SW1398cellsand lowest in COLO 205 and WiDr cells. The activity of SN-38 was 130 to 570 times than CPT-11[4].

In vivo: In COLO 320 xenografts, Irinotecan induced a maximum growth inhibition of 92% [4].A single dose of Irinotecan significantly increased amounts of topoisomerase I covalently bound to DNA in stomach, duodenum, colon and liver. Concomitantly, the Irinotecan-treated group exihibited significantly higher amounts of DNA strand breaks in colon mucosa cells compared to the control group [5].

References:
[1].  Tobin P, Clarke S, Seale J P, et al. The in vitro metabolism of irinotecan (CPT‐11) by carboxylesterase and β‐glucuronidase in human colorectal tumours[J]. British journal of clinical pharmacology, 2006, 62(1): 122-129.
[2]. Shingyoji M, Takiguchi Y, Watanabe‐Uruma R, et al. In vitro conversion of irinotecan to SN‐38 in human plasma[J]. Cancer science, 2004, 95(6): 537-540.
[3]. van Ark-Otte J, Kedde M A, Van Der Vijgh W J, et al. Determinants of CPT-11 and SN-38 activities in human lung cancer cells[J]. British journal of cancer, 1998, 77(12): 2171.
[4]. Jansen W J M, Zwart B, Hulscher S T M, et al. CPT-11 in human colon-cancer cell lines and xenografts: characterization of cellular sensitivity determinants[J]. International journal of cancer, 1997, 70(3): 335-340.
[5]. Na Y S, Jung K A, Kim S M, et al. The histone deacetylase inhibitor PXD101 increases the efficacy of irinotecan in in vitro and in vivo colon cancer models[J]. Cancer chemotherapy and pharmacology, 2011, 68(2): 389-398.

Chemical Properties

Physical AppearanceA solid
StorageStore at -20°C
M.Wt586.68
Cas No.97682-44-5
FormulaC33H38N4O6
Solubility>29.4mg/mL in DMSO
Chemical Name4,11-diethyl-4-hydroxy-3,14-dioxo-3,4,12,14-tetrahydro-1H-pyrano[3',4':6,7]indolizino[1,2-b]quinolin-9-yl [1,4'-bipiperidine]-1'-carboxylate
SDFDownload SDF
Canonical SMILESO=C(OC1)C(O)(CC)C2=C1C(N(CC3=C4N=C5C(C=C(OC(N6CCC(N7CCCCC7)CC6)=O)C=C5)=C3CC)C4=C2)=O
Shipping ConditionEvaluation sample solution: ship with blue ice. All other available sizes: ship with RT, or blue ice upon request.
General tipsFor obtaining a higher solubility, please warm the tube at 37°C and shake it in the ultrasonic bath for a while. Stock solution can be stored below -20°C for several months.

Protocol

Cell experiment [1]:

Cell lines

HT29, NMG64/84, COLO-357, MIA PaCa-2 and PANC-1 cells

Preparation method

The solubility of this compound in DMSO is >29.4mg/mL. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0.1-1000 μg/ml, 30 min

Applications

Irinotecan displayed concentration- and time-dependent cytotoxic effects in all tested cell lines. In COLO-357, MIA PaCa-2 and PANC-1 cells, irinotecan increased cell number in G0/G1 and decreased cell number in S- and G2-phase. Low concentration of irinotecan increased cell number in G2-phase in HT29 and NMG 64/84.

Animal experiment [2]:

Animal models

ICR male mice

Dosage form

Intraperitoneal injection, 100 mg/kg

Application

The time course of body weight change after Irinotecan (100 mg/kg i.p.) injection showed a significant dosing time-dependent difference (P

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[1]. HOFMANN C, BUTTENSCHOEN K, STRAETER J, et al. Pre-clinical evaluation of the activity of irinotecan as a basis for regional chemotherapy[J]. Anticancer research, 2005, 25(2A): 795-804.

[2]. Ohdo S, Makinosumi T, Ishizaki T, et al. Cell cycle-dependent chronotoxicity of irinotecan hydrochloride in mice[J]. Journal of Pharmacology and Experimental Therapeutics, 1997, 283(3): 1383-1388.

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