Dasatinib (BMS-354825) est un double Bcr-Abl et Src famille tyrosine kinase puissant et oralement actif avec des IC50s de 0,6 nM, 0,8 nM, respectivement. Dasatinib inhibe également Abl, Src, Fyn, c-Kit et c-KitD816V avec des IC50 de 2,8 nM, 79 nM et 37 nM, respectivement. Dasatinib induit également l'apoptose et l'autophagie. Dasatinib présente une activité puissante antitumorale et a le potentiel de traiter la leucémie myéloïde chronique (LMC).
Dasatinib (BMS-354825) ist ein hochwirksamer, ATP-kompetitiver, oral aktiver dualer Src/Bcr-Abl-Inhibitor mit starker Antitumor-Aktivität. Die Ki-Werte von 16 pM und 30 pM für Src bzw. Bcr-Abl.
Dasatinib (BMS-354825) is a highly potent, ATP competitive, orally active dual Src/Bcr-Abl inhibitor with potent antitumor activity. The Kis are 16 pM and 30 pM for Src and Bcr-Abl, respectively. Dasatinib inhibits Bcr-Abl and Src with IC50s of <1.0 nM and 0.5 nM, respectively. Dasatinib also induces apoptosis and autophagy.
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Dasatinib Chemical Structure
CAS No. : 302962-49-8
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Synergistic Decrease Bcl-2 Expression by the Combination of SAHA with Dasatinib in MCF-7 Cells.
Dasatinib purchased from MedChemExpress. Usage Cited in:
Chem Pharm Bull (Tokyo). 2017 Aug 1;65(8):768-775.
[Abstract]
Changes in Bcl-2 protein expression in MCF-7 cells after treatment with NSC 105014, Dasatinib or ZD1839 alone or in combination for 12 h. Expression of Bcl-2 protein is analyzed by western blotting analysis.
Western blot analysis of effects of Dasatinib (10 or 100nM) on c-Src, p-SrcY416, FAK and p-FAKY861 expression levels in KTC-1 cells and band intensities for p-SrcY416.
Drug combination effect on phosphorylation of AKT. Expression of phospho-AKT and total AKT in MOLM13 cells treated for 15 minutes with DMSO vehicle, PKC412 (2.5 nM), Dasatinib (165 nM), or a combination of both. Protein lysates are prepared from MOLM13 cells, and are analyzed via immunoblotting with antibodies to phospho-AKT and total AKT.
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Lck Fyn Blk
Description
Dasatinib (BMS-354825) is a highly potent, ATP competitive, orally active dual Src/Bcr-Abl inhibitor with potent antitumor activity. The Kis are 16 pM and 30 pM for Src and Bcr-Abl, respectively. Dasatinib inhibits Bcr-Abl and Src with IC50s of <1.0 nM and 0.5 nM, respectively[1]. Dasatinib also induces apoptosis and autophagy.
IC50 & Target[1]
Bcr-Abl
1.0 nM (IC50)
Src
0.5 nM (IC50)
lck
0.4 nM (IC50)
yes
0.5 nM (IC50)
c-kit
5.0 nM (IC50)
PDGFRβ
28 nM (IC50)
p38
100 nM (IC50)
Her1
180 nM (IC50)
Her2
710 nM (IC50)
FGFR-1
880 nM (IC50)
MEK
1700 nM (IC50)
In Vitro
Dasatinib demonstrates significant activity against Bcr-Abl, Src, Lck, Yes, c-Kit, PDGFRβ, p38, Her1, Her2, FGFR-1, and MEK with IC50s of <1.0, 0.50, 0.40, 0.50, 5.0, 28, 100, 180, 720, 880, and 1700 nM, respectively[1].
Dasatinib shows antiproliferative activities aversus K562 chronic myelogenous leukemia (CML), PC3 human prostate tumor, MDA-MB-231 human breast tumor, and WiDr human colon tumor cell lines with IC50s of <1.0 nM, 9.4 nM, 12 nM, and 52 nM, respectively[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Dasatinib Related Antibodies
In Vivo
Dasatinib (5 mg/kg and 50 mg/kg, qd×10d, 5 on-2 off) possesses potent antitumor activity and a high safety margin in a K562 xenograft model of chronic myelogenous leukemia (CML), demonstrating complete tumor regressions and low toxicity at multiple dose levels[1].
Dasatinib (10 mg/kg) has a pharmacokinetic profile appropriate for continued advancement into in vivo efficacy studies. Dasatinib (10 mg/kg) demonstrates favorable half-lives (t1/2s) of 3.3 and 3.1 h for i.v. and oral, respectively. The oral bioavailability (Fpo) in this study is 27%[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Animal Model:
Nude mice bearing K562 xenografts
Dosage:
5 mg/kg and 50 mg/kg
Administration:
Oral administration on a 5 day on and 2 day off schedule.
Result:
Showed partial tumor regressions after one treatment cycle and complete disappearance of the tumor mass by the end of drug treatment. No toxicity (animal deaths, lack of weight gain) was observed.
Animal Model:
Sprague-Dawley Rats
Dosage:
10 mg/kg (Pharmacokinetic Analysis)
Administration:
Oral and i.v.
Result:
Cmax of 13.2 and 0.5 μM for i.v. and oral, respectively.
Room temperature in continental US; may vary elsewhere.
Stockage
Powder
-20°C
3 years
4°C
2 years
In solvent
-80°C
2 years
-20°C
1 year
Solvant et solubilité
In Vitro:
DMSO : 125 mg/mL (256.14 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Preparing Stock Solutions
ConcentrationSolventMass
1 mg
5 mg
10 mg
1 mM
2.0491 mL
10.2457 mL
20.4914 mL
5 mM
0.4098 mL
2.0491 mL
4.0983 mL
10 mM
0.2049 mL
1.0246 mL
2.0491 mL
View the Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Protocol 4
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Taking 1 mL working solution as an example, add 100 μLDMSO stock solution (20.8 mg/mL) to 900 μLCorn oil, and mix evenly.
For the following dissolution methods, please prepare the working solution directly.
It is recommended to prepare fresh solutions and use them promptly within a short period of time. The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution.
If precipitation or phase separation occurs during preparation,
heat and/or sonication can be used to aid dissolution.
Protocol 1
Add each solvent one by one: 0.5% CMC-Na/saline water
Solubility: 50 mg/mL (102.46 mM); Suspended solution; Need ultrasonic
Protocol 2
Add each solvent one by one: 20% SBE-β-CD in Saline
Solubility: 2 mg/mL (4.10 mM); Suspended solution; Need ultrasonic
Protocol 3
Add each solvent one by one: 0.5% Methyl cellulose/0.5% Tween-80 in Saline water
Solubility: 6.67 mg/mL (13.67 mM); Suspended solution; Need ultrasonic
In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:
Dosage
mg/kg
Animal weight (per animal)
g
Dosing volume (per animal)
μL
Number of animals
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
%
DMSO+
%
+
%
Tween-80
+
%
Saline
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO,
. All of co-solvents are available by MedChemExpress (MCE).
, Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration:
mg/mL
Method for preparing stock solution:
mg
drug dissolved in
μL
DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take
μL DMSO stock solution, add
μL .
μL , mix evenly, next add
μL Tween 80, mix evenly, then add
μL Saline.
Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution
If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
[1]. Lombardo LJ, et al. Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem. 2004 Dec 30;47(27):6658-61.
[Content Brief]
[1]. Lombardo LJ, et al. Discovery of N-(2-chloro-6-methyl- phenyl)-2-(6-(4-(2-hydroxyethyl)- piperazin-1-yl)-2-methylpyrimidin-4- ylamino)thiazole-5-carboxamide (BMS-354825), a dual Src/Abl kinase inhibitor with potent antitumor activity in preclinical assays. J Med Chem. 2004 Dec 30;47(27):6658-61.
Complete Stock Solution Preparation Table
*Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles. Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Optional Solvent
ConcentrationSolventMass
1 mg
5 mg
10 mg
25 mg
DMSO
1 mM
2.0491 mL
10.2457 mL
20.4914 mL
51.2285 mL
5 mM
0.4098 mL
2.0491 mL
4.0983 mL
10.2457 mL
10 mM
0.2049 mL
1.0246 mL
2.0491 mL
5.1228 mL
15 mM
0.1366 mL
0.6830 mL
1.3661 mL
3.4152 mL
20 mM
0.1025 mL
0.5123 mL
1.0246 mL
2.5614 mL
25 mM
0.0820 mL
0.4098 mL
0.8197 mL
2.0491 mL
30 mM
0.0683 mL
0.3415 mL
0.6830 mL
1.7076 mL
40 mM
0.0512 mL
0.2561 mL
0.5123 mL
1.2807 mL
50 mM
0.0410 mL
0.2049 mL
0.4098 mL
1.0246 mL
60 mM
0.0342 mL
0.1708 mL
0.3415 mL
0.8538 mL
80 mM
0.0256 mL
0.1281 mL
0.2561 mL
0.6404 mL
100 mM
0.0205 mL
0.1025 mL
0.2049 mL
0.5123 mL
Dasatinib Related Classifications
Protein Tyrosine Kinase/RTKAutophagyApoptosis
Bcr-AblSrcAutophagyApoptosis
Help & FAQs
Do most proteins show cross-species activity?
Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.
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