Topotecan HCl

Catalog No.S1231

Topotecan HCl is a topoisomerase I inhibitor for MCF-7 Luc cells and DU-145 Luc cells with IC50 of 13 nM and 2 nM in cell-free assays, respectively.

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Topotecan HCl Chemical Structure

Topotecan HCl Chemical Structure
Molecular Weight: 457.91

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Product Information

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Product Description

Biological Activity

Description Topotecan HCl is a topoisomerase I inhibitor for MCF-7 Luc cells and DU-145 Luc cells with IC50 of 13 nM and 2 nM in cell-free assays, respectively.
Targets Topo I (DU-145 Luc cells) [1]
(Cell-free assay)
Topo I (MCF-7 Luc cells) [1]
(Cell-free assay)
IC50 2 nM 13 nM
In vitro Stronger drug activity of Topotecan is observed for DU-145 Luc and MCF-7 Luc cells. [1] Topotecan causes cytotoxicity during the course of DNA replication by stabilizing the covalent complex between topoisomerase I and DNA and preventing the religation of enzyme-linked single-strand DNA break. Topotecan stabilizes topoisomerase I/DNA cleavable complexes in radiation-resistant human B-lineage acute lymphoblastic leukemia (ALL) cells, causes rapid apoptotic cell death despite high-level expression of bcl-2 protein, and inhibits ALL cell clonogenic growth in a dose-dependent fashion. [2]
In vivo Animals inoculate s.c. with DU-145 Luc cells and then treated with Topotecan demonstrates significant tumor growth and regression as measured with calipers and luminescent imaging. The correlation coefficient is 0.75 for the control untreated group and 0.93 for the Topotecan-treated group. Similarly, tumor progression and regression are measurable using luminescent imaging for untreated and Topotecan-treated mice inoculated i.p. with MCF-7 Luc cells. [1] Topotecan elicited potent antileukemic activity in severe combined immune-deficiency (SCID) mouse models of human poor prognosis ALL. Topotecan markedly improved event-free survival of SCID mice challenged with otherwise fatal doses of humaln leukemia cells at systemic drug exposure levels. [2] Gliomas preferentially express TRAIL R2 and that treatment with Topotecan significantly up-regulates its expression. [3]
Features Topotecan is a water-soluble derivative of camptothecin.

Protocol(Only for Reference)

Cell Assay:

[1]

Cell lines MCF-7 Luc and DU-145 Luc cells
Concentrations 0 μg/mL - 0.692 μg/mL
Incubation Time 96 hours
Method

Topotecan is dissolved in sterile water to a stock concentration of 1 mg/mL, diluted to 6 μg/mL in cultured medium and then serially diluted 1:4 in opaque, white tissue culture-treated microplates to a final volume of 0.1 mL/well. MCF-7 Luc and DU-145 Luc cells are resuspended in 3×104 cells/mL in DMEM with high glucose containing 10% FBS and 0.5 mg/mL Geneticin; 100 μL of cells are added in each well. Plates are incubated for 4 days at 37 °C in 95% humidity/5% CO2. After incubation, 0.05 mL of 0.1 M HEPES buffer (pH 7.9) containing 50 μg/mL D-luciferin is added to each well. After incubation at room temperature for 10 minutes, the culture microplate is measured in a microplate luminometer and a molecular light imager. Results obtained with the microplate luminometer are calculated using no inhibition control wells without exogenous drug and maximum inhibition control wells containing ATP inhibitor. Results for the molecular light imager are similarly calculated using values obtained with a 5 minutes luminescent imager.

Animal Study:

[1]

Animal Models Mice with MCF-7 Luc or DU-145 Luc cells
Formulation PBS
Dosages 0.25 mg/mL
Administration Administered via i.p.

Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)

SpeciesMouseRatRabbitGuinea pigHamsterDog
Weight (kg)0.020.151.80.40.0810
Body Surface Area (m2)0.0070.0250.150.050.020.5
Km factor36128520
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Rat dose (mg/kg) = mouse dose (22.4 mg/kg) ×  mouse Km(3)  = 11.2 mg/kg
rat Km(6)
1

References

[1] Caceres G, et al. Anticancer Drugs. 2003, 14(7), 569-574.

[2] Uckun FM, et al. Blood. 1995. 85(10), 2817-2828.

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Clinical Trial Information( data from http://clinicaltrials.gov, updated on 2016-07-23)

NCT Number Recruitment Conditions Sponsor
/Collaborators
Start Date Phases
NCT02348398 Not yet recruiting Cervical Cancer M.D. Anderson Cancer Center|GlaxoSmithKline August 2016 Phase 2
NCT02822157 Not yet recruiting Ovarian Epithelial Cancer Universitaire Ziekenhuizen Leuven|AstraZeneca August 2016 Phase 2
NCT02566993 Not yet recruiting Small-cell Lung Cancer PharmaMar July 2016 Phase 3
NCT02813135 Recruiting Children, Adolescents and Young Adults With Refractory or Recurrent Malignancies Gustave Roussy, Cancer Campus, Grand Paris|National Cance  ...more Gustave Roussy, Cancer Campus, Grand Paris|National Cancer Institute, France June 2016 Phase 1|Phase 2
NCT02786719 Not yet recruiting Neuroblastoma Baylor College of Medicine|Texas Childrens Hospital June 2016 --

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Chemical Information

Download Topotecan HCl SDF
Molecular Weight (MW) 457.91
Formula

C23H23N3O5.HCl

CAS No. 119413-54-6
Storage 3 years -20℃powder
6 months-80℃in solvent
Synonyms NSC609699, Nogitecan HCl, SKFS 104864A
Solubility (25°C) * In vitro DMSO 92 mg/mL (200.91 mM)
Water 92 mg/mL (200.91 mM)
Ethanol <1 mg/mL (<1 mM)
In vivo Saline 30 mg/mL
* <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.
Chemical Name (4S)​-10-​[(dimethylamino)​methyl]​-​4-​ethyl-​4,​9-​dihydroxy-​1H-​pyrano[3',​4':6,​7]​indolizino[1,​2-​b]​quinoline-​3,​14(4H,​12H)​-​dione, hydrochloride (1:1)

Customer Product Validation(2)


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Rating
Source BMC Cancer, 2015, 10.1186/s12885-015-1231-z. Topotecan HCl purchased from Selleck
Method Western Blot
Cell Lines Ovcar5、Ovcar3、Ovcar8 cells
Concentrations 0.2 µM
Incubation Time 16 h
Results DNA damage was greatest with co-treatment in all cell lines, and the activation of CHEK1 activity upon TPT (topotecan) treatment was abrogated by co-treatment with PF477736.

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Rating
Source PLoS Genet 2014 10(1), e1004107. Topotecan HCl purchased from Selleck
Method MTS assay
Cell Lines aRMS tumor cells
Concentrations 0-1000000 nM
Incubation Time
Results To assess the extent to which the fusion gene mediates refractoriness to chemotherapy agents, we observed Pax3:Foxo1a to facilitate 2-4 fold refractoriness to clinical agents capable of causing double-stranded DNA breaks and mitotic arrest (topotecan) more so than agent inducing single-strand breaks (mafosfamide, the active metabolite of cyclophosphamide).

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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