| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| 25mg | |||
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| Other Sizes |
| Targets |
Bcr-Abl and Src family tyrosine kinases. Dasatinib is a potent and orally active ATP-competitive inhibitor of both Bcr-Abl and Src family kinases (IC50s: 0.6 nM for Bcr-Abl, 0.8 nM for Src). Metabolite M6 retains structural similarity to dasatinib but exhibits significantly reduced kinase inhibitory activity. Based on exposure levels, it is not expected to contribute significantly to in vivo activity.
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|---|---|
| ln Vitro |
Dicentrics and chromosome aberrations: In vivo studies indicate that the primary oxidative metabolites of dasatinib (M4, M5, M6, M20, M24) are pharmacologically active but with significantly higher (less potent) IC50s for Src and Bcr-Abl kinase inhibition compared to the parent drug. Cell-based IC50s for these metabolites suggest they are not expected to contribute substantially toward the in vivo anti-leukemic activity.
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| ln Vivo |
In humans, dasatinib is extensively metabolized, with M4 (N-dealkylation), M5 (N-oxidation), M6 (carboxylic acid formation), M20, and M24 (hydroxylation) as the primary oxidative metabolites. The exposures of these metabolites, combined with their cell-based IC50 values for Src and Bcr-Abl inhibition, indicate they are not expected to contribute meaningfully to in vivo pharmacological activity.
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| Enzyme Assay |
Cell-free kinase inhibition assays are performed using recombinant human Bcr-Abl and Src kinases (0.5-2 nM) in a 50 uL reaction mix containing 50 mM HEPES (pH 7.5), 10 mM MgCl2, 2 mM MnCl2, 1 mM DTT, 0.01% BSA, and 10 uM ATP. Varying concentrations of Dasatinib metabolite M6 (0.1 nM to 10 uM) are added, and the reaction is initiated by adding a biotinylated peptide substrate. After 60 min at 30degC, the reaction is terminated with EDTA, and phosphorylation is detected by time-resolved fluorescence (TR-FRET) using an Eu-labeled anti-phosphotyrosine antibody.
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| Cell Assay |
K562 human chronic myelogenous leukemia (CML) cells (BCR-ABL-positive) are seeded in 96-well plates (2 × 10⁴ cells/well) in RPMI-1640 with 10% FBS. Varying concentrations of Dasatinib metabolite M6 (1 nM to 10 uM) are added, and cells are incubated for 72 h at 37degC, 5% CO2. Cell viability is measured using the CellTiter-Glo luminescent assay. The IC50 is calculated from dose-response curves. Bcr-Abl autophosphorylation (Tyr412) is assessed by Western blotting after 2 h treatment.
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| Animal Protocol |
Not applicable (metabolite standard, not typically administered in efficacy studies). For PK studies, male Sprague-Dawley rats are dosed orally with dasatinib (5-10 mg/kg). Blood samples are collected at predetermined intervals (0, 0.5, 1, 2, 4, 8, 12, 24 h). Plasma is processed, and concentrations of Dasatinib and its metabolite M6 are quantified by LC-MS/MS using stable isotope-labeled internal standards. Pharmacokinetic parameters (Cmax, Tmax, AUC, t½) are calculated.
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| ADME/Pharmacokinetics |
Dasatinib metabolite M6 is used as an analytical reference standard for LC-MS/MS quantification. The parent drug dasatinib is well absorbed orally (bioavailability ~80%), with a terminal half-life of 3-5 h. It is highly protein bound (>95%) and primarily metabolized by CYP3A4. The M6 metabolite (carboxylic acid derivative) results from further oxidation and has a longer plasma half-life (~15-20 h) but much lower potency.
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| Toxicity/Toxicokinetics |
The labeled D8 version is not for human use. Parent drug dasatinib has a boxed warning for QT prolongation, severe bleeding, and fetal harm. Common AEs: myelosuppression (neutropenia, thrombocytopenia, anemia), fluid retention (peripheral edema, pleural effusion), diarrhea, headache, and rash. Metabolite M6 is considered a non-contributory metabolite in terms of clinical efficacy but may be monitored for toxicity.
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| References | |
| Additional Infomation |
Dasatinib (Sprycel) was FDA-approved in 2006 for CML and Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). Metabolite M6 is primarily a research reference standard for LC-MS/MS quantification in DMPK and bioequivalence studies. It is a key compound for understanding the ADME (absorption, distribution, metabolism, excretion) profile of dasatinib and for safety testing of related metabolites.
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| Molecular Formula |
C22H24N7O3SCL
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|---|---|
| Molecular Weight |
501.98906
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| Exact Mass |
501.135
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| CAS # |
910297-53-9
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| PubChem CID |
11854012
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| Appearance |
White to off-white solid powder
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| Density |
1.461g/cm3
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| Index of Refraction |
1.695
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| LogP |
3.554
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
714
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
VMCDXJFWSYUNPO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H24ClN7O3S/c1-13-4-3-5-15(23)20(13)28-21(33)16-11-24-22(34-16)27-17-10-18(26-14(2)25-17)30-8-6-29(7-9-30)12-19(31)32/h3-5,10-11H,6-9,12H2,1-2H3,(H,28,33)(H,31,32)(H,24,25,26,27)
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| Chemical Name |
2-[4-[6-[[5-[(2-chloro-6-methylphenyl)carbamoyl]-1,3-thiazol-2-yl]amino]-2-methylpyrimidin-4-yl]piperazin-1-yl]acetic acid
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~199.21 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (4.98 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (4.98 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (4.98 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9921 mL | 9.9604 mL | 19.9207 mL | |
| 5 mM | 0.3984 mL | 1.9921 mL | 3.9841 mL | |
| 10 mM | 0.1992 mL | 0.9960 mL | 1.9921 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.
Calculation results
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.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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