Dasatinib hydrochloride |
| رقم الكتالوجGC35812 |
Dasatinib (BMS-354825) هيدروكلوريد هو مثبط مزدوج قوي للغاية ، منافس لـ ATP ، نشط عن طريق الفم Src / Bcr-Abl مع نشاط قوي مضاد للأورامKis هي 16 مساءً و 30 مساءً لـ Src و Bcr-Abl ، على التواليهيدروكلوريد Dasatinib يثبط Bcr-Abl و Src مع IC50s <1.0 نانومتر و 0.5 نانومتر ، على التوالييحفز هيدروكلوريد داساتينيب أيضًا موت الخلايا المبرمج والالتهام الذاتي
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 854001-07-3
Sample solution is provided at 25 µL, 10mM.
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Dasatinib hydrochloride is a potent and dual AblWT/Src inhibitor IC50 of 0.6 nM/0.8 nM respectively; also inhibits c-KitWT/c-KitD816V with IC50 of 79 nM/37 nM. IC50: 0.6 nM/0.8 nM (AblWT/Src)[1]IC50: 79 nM/37 nM (c-KitWT/c-KitD816V)[2]
Dasatinib potently inhibits wild-type Abl kinase and all mutants except T315I over a narrow range (IC50≤1.7 nM). Dasatinib (IC50: 0.8 nM) displays 325-fold greater potency compared with Imatinib against cells expressing wild-type Bcr-Abl in Ba/F3 cells[1].
Daily treatment with Dasatinib (50 mg/kg) is initiated on day 10. Using this approach, a significant inhibition of BCPAP orthotopic tumor growth is observed 6 days after treatment (day 16, P=0.014), which is sustained through days 23 and 29 (P=0.0003), compared with vehicle-treated mice[3]. Metabolism studies of Dasatinib (50 mg/kg) in rat suggested that Dasatinib is the major circulating component, whereas multiple metabolites contributed to the remaining 40-60% of the sample radioactivity at 4 h post dose[4].
[1]. O'Hare T, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinase domain mutants. Cancer Res. 2005 Jun 1;65(11):4500-5. [2]. Shah NP, et al. Dasatinib (BMS-354825) inhibits KITD816V, an imatinib-resistant activating mutation that triggers neoplastic growth in most patients with systemic mastocytosis. Blood. 2006 Jul 1;108(1):286-91. [3]. Chan CM, et al. Targeted inhibition of Src kinase with dasatinib blocks thyroid cancer growth and metastasis. Clin Cancer Res. 2012 Jul 1;18(13):3580-91. [4]. Shen Z, et al. Metabolite profiling of dasatinib dosed to Wistar Han rats using automated dried blood spot collection. J Pharm Biomed Anal. 2012 Aug-Sep;67-68:92-7.
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Cell experiment: |
Ba/F3 cell lines are plated in triplicate and incubated with escalating concentrations of STI571, AMN107, or Dasatinib for 72 hours. Proliferation is measured using a methanethiosulfonate-based viability assay (CellTiter96 Aqueous One Solution Reagent). IC50 and IC90 values are reported as the mean of three independent experiments done in quadruplicate. The inhibitor concentration ranges for IC50 and IC90determinations are 0 to 2,000 nM (STI571 and AMN107) or 0 to 32 nM (Dasatinib). The STI571 concentration range is extended to 6,400 nM for mutants with IC50>2,000 nM. The Dasatinib concentration range is extended to 200 nM for mutant T315I. |
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Animal experiment: |
Mice[3]Male athymic nude mice (25 grams; 5-week old) are used. Dasatinib (50 mg/kg) is prepared for daily oral gavage (5 d/wk) in 80 mM sodium citrate buffer, pH 3.0. For the orthotopic murine model, mice are randomized on day 10 based on bioluminescence activity to receive drug or vehicle. In the metastatic murine model, mice receives dasatinib or vehicle, as described earlier, starting 2 days before intracardiac injection (pretreatment), or on day 11 following randomization (posttreatment).Rats[4]Dasatinib is dosed to male Wistar-Han (WH) rats at 50 mg/kg orally in 0.5% methylcellulose. The automated rat blood collection device is programmed to collect 200 μL of blood at predetermined intervals. At each time point, the accusampler is programmed to directly spot 20 μL of blood twice (two spots) onto the DBS card. The remaining 160 μL of liquid blood is collected into sodium EDTA-containing tubes. Plasma samples are obtained after immediate centrifugation of blood at 11,000 rpm for 5 min. The plasma samples are stored at −80°C until analyses. The DBS samples are dried under room temperature for a minimum of 2 h and stored in a plastic bag in the dessicator until sample analysis. |
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References: [1]. O'Hare T, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant STI571-resistant Abl kinase domain mutants. Cancer Res. 2005 Jun 1;65(11):4500-5. |
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| Cas No. | 854001-07-3 | SDF | |
| Canonical SMILES | O=C(C1=CN=C(S1)NC2=NC(C)=NC(N3CCN(CC3)CCO)=C2)NC4=C(C=CC=C4Cl)C.[H]Cl | ||
| Formula | C22H27Cl2N7O2S | M.Wt | 524.47 |
| الذوبان | DMSO: 15 mg/mL (28.60 mM and warming); Water: 10 mg/mL (19.07 mM) | Storage | Store at 2-8°C,stored under nitrogen |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9067 mL | 9.5334 mL | 19.0669 mL |
| 5 mM | 0.3813 mL | 1.9067 mL | 3.8134 mL |
| 10 mM | 0.1907 mL | 0.9533 mL | 1.9067 mL |
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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
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- Purity: >99.00%
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