1. Cell Cycle/DNA Damage
  2. Topoisomerase

Exatecan Mesylate (Synonyms: DX8951f)

Cat. No.: HY-13631A Purity: 98.09%
Handling Instructions

Exatecan Mesylate is a water soluble topoisomerase I inhibitor, with an IC50 of 2.2 μM (0.975 μg/mL), and can be used in cancer research.

For research use only. We do not sell to patients.
Exatecan Mesylate Chemical Structure

Exatecan Mesylate Chemical Structure

CAS No. : 169869-90-3

Size Price Stock Quantity
10 mM * 1 mL in DMSO USD 1375 In-stock
1 mg USD 660 In-stock
5 mg USD 1176 In-stock
10 mg USD 1800 In-stock
50 mg   Get quote  
100 mg   Get quote  

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Other Forms of Exatecan Mesylate:

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

Exatecan Mesylate is a water soluble topoisomerase I inhibitor, with an IC50 of 2.2 μM (0.975 μg/mL), and can be used in cancer research.

IC50 & Target

IC50: 2.2 μM (topoisomerase I)[1]

In Vitro

Exatecan Mesylate is a potent topoisomerase I inhibitor, with an IC50 of 0.975 μg/mL. Exatecan Mesylate (DX-8951f) significantly inhibits the proliferation of several cancer cell lines, with mean GI50s of 2.02 ng/mL, 2.92 ng/mL, 1.53 ng/mL, and 0.877 ng/mL for breast cancer cells, colon cancer cells, stomach cancer cells and lung cancer cells, respectively[1]. Exatecan Mesylate (DX-8951f) displays cytotoxic activities against PC-6, PC-6/SN2-5 cells, with mean GI50s of 0.186 and 0.395 ng/mL, respctively. Exatecan Mesylate (34 nM) stabilizes DNA-TopoI complexes in PC-6 and PC-6/SN2-5 cells[3].

In Vivo

Exatecan Mesylate (DX-8951f, 3.325-50 mg/kg, i.v.) exhibits antitumor activities in the mice model bearing tumor cells, without toxic death[1]. Exatecan Mesylate (15, 25 mg/kg, i.v.) hightly inhibits MIA-PaCa, BxPC-3 primary tumor growth in the MIA-PaCa-2 early-stage model and early-stage model of BxPC-3. Exatecan Mesylate (15, 25 mg/kg, i.v.) also significantly suppresses BxPC-3 lymphatic metastasis and completely eliminates lung metastasis in the BxPC-3 late-stage cancer model[2].

Clinical Trial
References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 1.8813 mL 9.4065 mL 18.8129 mL
5 mM 0.3763 mL 1.8813 mL 3.7626 mL
10 mM 0.1881 mL 0.9406 mL 1.8813 mL
Please refer to the solubility information to select the appropriate solvent.
Kinase Assay
[3]

Cells (5×106) are lysed with SDS buffer (10 mM HEPES, 2 mM orthovanadate, 10 mM NaF, 10 mM pyrophosphate, 1 mMPMSF, 10 µg/mL leupeptin, 10% 2-mercaptoethanol, 10% glycerol,8% SDS, 42 mM Tris-HCl, 0.002% bromophenol blue, pH 7.4). Protein in the whole cell lysates is separated in 7.5% polyacryl-amide gel and blotted onto nitrocellulose membrane. The membrane is treated with anti-Topo I human antibody and subsequently, with horseradish peroxidase-conjugated protein A. The Topo I-specific band is detected with ECL reagents. To obtain a nuclear extract, cells (5×107) are washed with ice-cold buffer (2 mM K2HPO4, 5 mM MgCl2, 150 mM NaCl, 1 mM EGTA, 0.1 mM dithiothreitol), resuspended in buffer containing 0.35% Triton-X100 and PMSF and then incubated on ice for 10 min. The resulting lysates are centrifuged, and precipitates are then incubated with buffer containing 0.35 M NaCl for 1 hr at 4°C. After centrifugation (18,000g, 10 min), the protein concentration of the supernatant (nuclear extract) is determined using a protein assay kit. The same amount of nuclear protein is analyzed by Western blotting analysis using anti-Topo I antibody[3]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Cell Assay
[1]

Exatecan Mesylate is dissolved in DMSO, and diluted with the medium.

Growth inhibition experiments are carride out in 96-well flat-bottomed microplates, and the amount of viable cell at the end of the incubation is determined by MTT assay. Thus, 500-20000 cells/well in 150 μL of medium are plated and grown for 24 h (P388, CCRF-CEM and K562 cells for 4h), the drug (including Exatecan Mesylate, in 150 μL medium/well), or the medium alone as a control, is added, and the cells are cultured for an additional 3 days. After addition of MTT (20 μL/well, 5 mg/mL in phosphate-buffered saline), the plates are incubated for 4 h and centrifuged at 800 g for 5 min, then the medium is removed and the blue dye formed is dissolved in 150 μL of DMSO. the absorbance is measured at 540 nm using a Microplate Reader model 3550[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[2]

Exatecan Mesylate is diluted in water and administered i.v.

At 3 weeks after BxPC-3-GFP and MIA-PaCa-2-GFP orthotopic implantation, mice are randomized into five different groups of 5 mice each for treatment purposes. Group 1 serves as the negative control and does not receive any treatment. Groups 2 and 3 are treated with Exatecan Mesylate at 25 and 15 mg/kg/dose, respectively. Groups 4 and 5 receive gemcitabine treatments at 300 and 150 mg/kg/dose, respectively. At 6 weeks after BxPC-3-GFP orthotopic implantation, mice are randomized into three different groups of 20 mice each for treatment purposes. Group 1 serves as the negative control and does not receive any treatment. Group 2 is treated with 25 mg/kg/dose Exatecan Mesylate and group 3 receives 300 mg/kg/dose gemcitabine. Dosing for both drugs is performed once a week for 3 weeks, discontinued for 2 weeks, and then continued for another 3 weeks. In both early and late cancer models, primary tumor size and body weights are measured once a week. Tumor volumes are calculated using the formula a × b2 × 0.5, where a and b represent the larger and smaller diameters, respectively. At the termination of the studies, mice are sacrificed and explored. Final tumor weights and direct GFP images of primary tumor and metastases are recorded for each mouse. The tumor growth IR is calculated using the formula IR (%) = (1 − TWt/TWc) × 100, where TWt and TWc are the mean tumor weight of treated and control groups, respectively[2]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

531.55

Formula

C₂₅H₂₆FN₃O₇S

CAS No.

169869-90-3

SMILES

O=S(C)(O)=O.O=C1[[email protected]](O)(CC)C2=C(CO1)C(N3CC4=C5C6=C(CC[[email protected]@H]5N)C(C)=C(F)C=C6N=C4C3=C2)=O

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: 15.3 mg/mL; H2O: 6 mg/mL (Need ultrasonic and warming)

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 98.09%

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Product Name:
Exatecan Mesylate
Cat. No.:
HY-13631A
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