Topotecan HCl (SKF 104864A)

Alias: 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
Cat No.:V1392 Purity: ≥98%
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.
Topotecan HCl (SKF 104864A) Chemical Structure CAS No.: 119413-54-6
Product category: Topoisomerase
This product is for research use only, not for human use. We do not sell to patients.
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Purity & Quality Control Documentation

Purity: ≥98%

Product 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. In cell-free assays, it inhibits topoisomerase I in MCF-7 Luc and DU-145 Luc cells with IC50 values of 13 nM and 2 nM, respectively. A semisynthetic derivative of camptothecin with antitumor properties is topotecan. Topotecan selectively stabilizes topoisomerase I-DNA covalent complexes during the S phase of the cell cycle. This prevents topoisomerase I-mediated single-strand DNA breaks from religating and creates potentially fatal double-strand DNA breaks when the DNA replication machinery comes into contact with the complexes.

Biological Activity I Assay Protocols (From Reference)
Targets
Topo I (DU-145 Luc cells) ( IC50 = 2 nM ); Topo I (MCF-7 Luc cells) ( IC50 = 13 nM )
ln Vitro

In vitro activity: Topotecan is observed to have stronger drug activity for MCF-7 Luc and DU-145 Luc cells. [1] By stabilizing the covalent complex between topoisomerase I and DNA and inhibiting the religation of enzyme-linked single-strand DNA breaks, topotecan causes cytotoxicity during DNA replication. In radiation-resistant human B-lineage acute lymphoblastic leukemia (ALL) cells, topotecan stabilizes topoisomerase I/DNA cleavable complexes, induces rapid apoptotic cell death despite high-level expression of bcl-2 protein, and dose-dependently suppresses the clonogenic growth of ALL cells. [2]

ln Vivo
Measuring tumor growth and regression with calipers and luminescent imaging, animals given DU-145 Luc cells intraperitoneally and treated with topotecan showed notable results. Topotecan-treated group's correlation coefficient is 0.93, while the control group's is 0.75. For both untreated and Topotecan-treated mice injected intraperitoneally (i.p.) with MCF-7 Luc cells, tumor growth and regression can be quantified through luminescent imaging.[1] In mice with severe combined immune deficiency (SCID), a model for human ALL with a poor prognosis, topotecan demonstrated strong antileukemic activity. When SCID mice were exposed to doses of humaln leukemia cells at systemic drug exposure levels, topotecan significantly increased their event-free survival.[2] Topotecan treatment significantly up-regulates the expression of TRAIL R2, which is preferentially expressed by gliomas.[3]
Cell Assay
Topotecan is first diluted to 6 μg/mL in cultured medium after being dissolved in sterile water to a stock concentration of 1 mg/mL. The final volume of each opaque, white tissue culture-treated microplate is achieved by serially diluting the solution 1:4 until it is 0.1 mL/well. 100 μL of cells are added to each 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. Plates are incubated for four days at 37 °C with 5% CO2 and 95% humidity. Each well receives 0.05 mL of 0.1 M HEPES buffer (pH 7.9) containing 50 μg/mL D-luciferin after incubation. The culture microplate is measured in a molecular light imager and a microplate luminometer after being incubated at room temperature for ten minutes. The microplate luminometer's results are computed using maximum inhibition control wells that contain an ATP inhibitor and no inhibition control wells that do not contain an exogenous drug. The values acquired with a 5-minute luminescent imager are used in a similar manner to calculate the results for the molecular light imager.
Animal Protocol
Mice: We used SK-N-BE, SH-SY5Y, KHOS, and RH30 for subcutaneous xenograft studies. The inguinal fat pad of each nonobese diabetic/severe combined immune deficient (NOD/SCID) mouse is subcutaneously implanted with 1×106 cells. The animals are divided into 4 groups at random and given oral gavage treatment every day once the tumors have grown to a diameter of 0.5 cm. The animals are divided into four groups: combination (TP + PZ; 1 mg/kg Topotecan Hydrochloride + 150 mg/kg Pazopanib), LDM Topotecan (1 mg/kg Topotecan), and Pazopanib (PZ; 150 mg/kg Pazopanib). In the KHOS osteosarcoma model, PZ is substituted with a weekly oral dose of either Pulse TP (15 mg/kg Topotecan) or pulse Topotecan in order to compare the two. Tumors with a diameter greater than 2.0 cm or animals exhibiting symptoms of morbidity are the endpoint criteria. Up until the endpoint or sacrifice, the tumor sizes are measured every day. Using calipers, the long (D) and short (d) diameters are measured. To compute tumor volume (cm3), use the formula V=0.5×D×d2. The animals are sacrificed by cervical dislocation when the treatment's endpoint is reached.
References

[1]. Anticancer Drugs . 2003 Aug;14(7):569-74.

[2]. Blood . 1995 May 15;85(10):2817-28.

[3]. J Neurooncol . 2005 Jan;71(1):19-25.

[4]. J Nucl Med . 2012 Jul;53(7):1146-54.

[5]. Cancer Chemother Pharmacol . 1998;41(5):385-90.

These protocols are for reference only. InvivoChem does not independently validate these methods.
Physicochemical Properties
Molecular Formula
C23H23N3O5.HCL
Molecular Weight
457.91
Exact Mass
457.14
Elemental Analysis
C, 60.33; H, 5.28; Cl, 7.74; N, 9.18; O, 17.47
CAS #
119413-54-6
Appearance
Yellow solid powder
SMILES
CC[C@@]1(C2=C(COC1=O)C(=O)N3CC4=CC5=C(C=CC(=C5CN(C)C)O)N=C4C3=C2)O.Cl
InChi Key
DGHHQBMTXTWTJV-BQAIUKQQSA-N
InChi Code
InChI=1S/C23H23N3O5.ClH/c1-4-23(30)16-8-18-20-12(9-26(18)21(28)15(16)11-31-22(23)29)7-13-14(10-25(2)3)19(27)6-5-17(13)24-20;/h5-8,27,30H,4,9-11H2,1-3H3;1H/t23-;/m0./s1
Chemical Name
(19S)-8-[(dimethylamino)methyl]-19-ethyl-7,19-dihydroxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2,4(9),5,7,10,15(20)-heptaene-14,18-dione;hydrochloride
Synonyms
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
HS Tariff Code
2934.99.9001
Storage

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Shipping Condition
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
Solubility Data
Solubility (In Vitro)
DMSO: 92~100 mg/mL (200.9~218.4 mM)
Water: <1 mg/mL
Ethanol: ~92 mg/mL (~200.9 mM)
Solubility (In Vivo)
Saline: 30 mg/mL
 (Please use freshly prepared in vivo formulations for optimal results.)
Preparing Stock Solutions 1 mg 5 mg 10 mg
1 mM 2.1838 mL 10.9192 mL 21.8384 mL
5 mM 0.4368 mL 2.1838 mL 4.3677 mL
10 mM 0.2184 mL 1.0919 mL 2.1838 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.

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Note: Chemical formula is case sensitive: C12H18N3O4  c12h18n3o4
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Working concentration mg/mL;

Method for preparing DMSO stock solution mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.

Method for preparing in vivo formulation:Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.

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Clinical Trial Information
NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT02030964 Active
Recruiting
Drug: Topotecan
Drug: DFMO
Neuroblastoma New Approaches to Neuroblastoma
Therapy Consortium
December 2013 Phase 1
NCT02298348 Active
Recruiting
Drug: Topotecan
Drug: Sorafenib
Neuroblastoma New Approaches to Neuroblastoma
Therapy Consortium
April 2015 Phase 1
NCT03600649 Active
Recruiting
Drug: Topotecan
Drug: Seclidemstat
Ewing Sarcoma
Myoepithelial Tumor
Salarius Pharmaceuticals, LLC June 4, 2018 Phase 1
NCT02487095 Active
Recruiting
Drug: Topotecan
Drug: VX-970
(M6620)
Small Cell Lung Carcinoma
Ovarian Neoplasms
National Cancer Institute
(NCI)
July 30, 2015 Phase 1
Phase 2
NCT00638898 Active
Recruiting
Drug: topotecan hydrochloride
Drug: busulfan
Solid Tumor
Ewing Sarcoma
City of Hope Medical Center February 26, 2007 Phase 1
Biological Data
  • Internucleosomal DNA fragmentation in topotecan-treated B-lineage ALL cells. Blood . 1995 May 15;85(10):2817-28.
  • (A and B) Ultrastructural features of topotecan treated ALL cells undergoing apoptosis. Blood . 1995 May 15;85(10):2817-28.
  • Nanomolar concentrations of topotecan induce apoptotic cell death of radiation-resistant RS4;11 leukemia cells expressing high levels of bcl-2 protein. Blood . 1995 May 15;85(10):2817-28.
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