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    Topotecan HCl (SKF 104864A)
    Topotecan HCl (SKF 104864A)

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    This product is for research use only, not for human use. We do not sell to patients.
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    InvivoChem Cat #: V1392
    CAS #: 119413-54-6 Purity ≥98%

    Description: Topotecan HCl (formerly known as NSC609699, Nogitecan, NSC-609699, SKFS-104864A; trade name: Hycamtin), an FDA approved drug for cancer treatment, is a topoisomerase I inhibitor with potent antineoplastic activity. It inhibits topoisomerase I in MCF-7 Luc and DU-145 Luc cells with IC50 of 13 nM and 2 nM in cell-free assays, respectively. Topotecan is a semisynthetic derivative of camptothecin with antitumor activity. During the S phase of the cell cycle, topotecan selectively stabilizes topoisomerase I-DNA covalent complexes, inhibiting religation of topoisomerase I-mediated single-strand DNA breaks and producing potentially lethal double-strand DNA breaks when complexes are encountered by the DNA replication machinery.

    References: Anticancer Drugs. 2003 Aug;14(7):569-74; Blood. 1995 May 15;85(10):2817-28.

    Related CAS#: 123948-87-8 (free base); 119413-54-6 (HCl);

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    Molecular Weight (MW)457.91
    CAS No.119413-54-6 (HCl);
    Storage-20℃ for 3 years in powder form
    -80℃ for 2 years in solvent
    Solubility (In vitro)DMSO: 92 mg/mL (200.9 mM)
    Water: <1 mg/mL
    Ethanol: 92 mg/mL (200.9 mM)
    Solubility (In vivo)Saline: 30 mg/mL 

    NSC609699; SKF-104864-A; NSC 609699; SKF 104864 A; NSC-609699; SKF S104864A; Nogitecan HCl; SKFS 104864A; SKF104864A; TOPO. Hycamtamine; Hycamtin Hydrochloride; Nogitecan Hydrochloride; Topotecan; Nogitecan Hydrochloride; Trade name: Hycamtin.

    Chemical Name: (S)-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 

    SMILES Code: O=C1[[email protected]](O)(CC)C2=C(CO1)C(N3CC4=CC5=C(CN(C)C)C(O)=CC=C5N=C4C3=C2)=O.[H]Cl

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    In Vitro

    In vitro activity: Stronger drug activity of Topotecan is observed for DU-145 Luc and MCF-7 Luc cells. 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.

    Cell Assay: 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.

    In VivoAnimals 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. 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. Gliomas preferentially express TRAIL R2 and that treatment with Topotecan significantly up-regulates its expression.
    Animal modelMice with MCF-7 Luc or DU-145 Luc cells
    Formulation & DosageDissolved in PBS; 0.25 mg/mL;  i.p. injection

    Anticancer Drugs. 2003 Aug;14(7):569-74; Blood. 1995 May 15;85(10):2817-28.

    These protocols are for reference only. InvivoChem does not independently validate these methods.


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