Dasatinib

For research use only.

Catalog No.S1021 Synonyms: BMS-354825

386 publications

Dasatinib Chemical Structure

CAS No. 302962-49-8

Dasatinib (BMS-354825) is a novel, potent and multi-targeted inhibitor that targets Abl, Src and c-Kit, with IC50 of <1 nM, 0.8 nM and 79 nM in cell-free assays, respectively. Dasatinib induces autophagy and apoptosis with anti-tumor activity.

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Selleck's Dasatinib has been cited by 386 publications

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Choose Selective Src Inhibitors

Biological Activity

Description Dasatinib (BMS-354825) is a novel, potent and multi-targeted inhibitor that targets Abl, Src and c-Kit, with IC50 of <1 nM, 0.8 nM and 79 nM in cell-free assays, respectively. Dasatinib induces autophagy and apoptosis with anti-tumor activity.
Targets
Abl [1]
(Cell-free assay)
Src [1]
(Cell-free assay)
c-Kit (D816V) [2]
(Cell-free assay)
c-Kit (wt) [2]
(Cell-free assay)
0.6 nM 0.8 nM 37 nM 79 nM
In vitro

Dasatinib is more effective than imatinib in inhibiting the proliferation of Ba/F3 cells expressing wild-type Bcr-Abl and Bcr-Abl mutants, with the exception of T315I. Dasatinib has a two-log (∼325-fold) increased potency relative to imatinib. Dasatinib potently inhibits wild-type Abl kinase and all mutants except T315I over a narrow range. Dasatinib directly targets wild-type and mutant Abl kinase domains and inhibits autophosphorylation and substrate phosphorylation in a concentration-dependent manner. Dasatinib displays 325-fold greater potency compared with imatinib against cells expressing wild-type Bcr-Abl. [1] The percent of colonies of TgE bone marrow cells are decreased from 100% in untreated wells to 4.12% in Dasatinib treated wells. In the presence of Dasatinib, the difference in the percentage of colonies formed by WT and TgE bone marrow cells is statistically significant. Expression of LMP2A is able to promote B lymphocyte survival and proliferation, which can be inhibited by targeting Lyn and/or c-Abl kinases through Dasatinib. [3] Dasatinib treatment inhibits Src signaling, decreases growth, and induces cell cycle arrest and apoptosis in a subset of thyroid cancer cells. Treatment with increasing doses of Dasatinib (0.019 μM to 1.25 μM) for 3 days inhibits the growth of the C643, TPC1, BCPAP, and SW1736 cell lines by about 50% at low nanomolar concentrations, while higher concentrations are required to inhibit the growth of the K1 cell line. Treatment with 10 nM or 50 nM Dasatinib results in a 9-22% increase of cells in the G1 population among BCPAP and SW1736 and K1 cells, and a corresponding 7-18% decrease in the percentage of cells in the S phase. [4]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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GAK NY[5TXZTT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= NHvRfmJKSzVyPUOxMlI3QDZizszN NVjMZlEyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTR{MT:nQnNCVkeHUkyvZV4>
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HCC1187 NIfzfoRIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= Mme4TWM2OD1|NT64NFUzKM7:TR?= NUTaeWdWRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTR{MT:nQnNCVkeHUkyvZV4>
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JVM-3 NFjveXpIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NWfYVoJvUUN3ME2zO{4zOzN6IN88US=> M1jk[lxiKHSjcnfleF0oZ2KuYX7rK{BpemWoPTfoeJRxezpxL4f3e{5m[mlwYXOueYsw[2inbXLsM4NwdXCxdX7kY5JmeG:{dG;jZZJlN0OKRV3CUFE1OjFxJ{7TRW5ITVJ:L3G+
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COR-L279 MYfHdo94fGhiSX7obYJqfGmxbjDBd5NigQ>? NWS5e|REUUN3ME20NE4zQDVzIN88US=> NVzEdZdrRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTR{MT:nQnNCVkeHUkyvZV4>
DEL MkDwS5Jwf3SqIFnubIljcXSrb36gRZN{[Xl? MnPETWM2OD12MT65NFg3KM7:TR?= MY[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxOFIyNyd-U1HOS2VTRC:jPh?=
NCI-H1395 NIrRd4FIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NE\jeoxKSzVyPUSyMlAyPjNizszN NUXFOYEyRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTR{MT:nQnNCVkeHUkyvZV4>
MHH-NB-11 NVHTbJRFT3Kxd4ToJGlvcGmkaYTpc44hSXO|YYm= MlP4TWM2OD12Mz6wPFE5KM7:TR?= NVHydlNKRGFidHHy[4V1RSehYnzhcosoKGi{ZX[9K4h1fHC|Oj:ve5d4NmWkaT7hZ{52cy:laHXtZoww[2:vcH;1coRgemWyb4L0Y4NiemRxQ1jFUWJNOTR{MT:nQnNCVkeHUkyvZV4>
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NEC8 NFLWTZFIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= NVnTSHBUUUN3ME20OE4{OzZizszN MW[8ZUB1[XKpZYS9K39jdGGwazegbJJm\j1paIT0dJM7Ny:5d4eu[YJqNmGlLoXrM4Np\W2kbD;jc41xd3WwZG;y[ZBwenShY3Hy[E9EUEWPQlyxOFIyNyd-U1HOS2VTRC:jPh?=
COLO-684 NF\1NIxIem:5dHigTY5pcWKrdHnvckBCe3OjeR?= MVHJR|UxRTR4LkKyOVgh|ryP MoHEQIEhfGG{Z3X0QUdg[myjbnunJIhz\WZ;J3j0eJB{Qi9xd4f3MoVjcS6jYz71b{9kcGWvYnyvZ49ueG:3bnTfdoVxd3K2X3PhdoQwS0iHTVLMNVQzOS9pPmPBUmdGWjxxYU6=
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... Click to View More Cell Line Experimental Data

Assay
Methods Test Index PMID
Western blot
phospho-c-Abl(Tyr245) / phospho-c-Src(Tyr416); 

PubMed: 23049975     


Protein levels of phosphorylated c-Abl (Tyr245), c-Abl, phosphorylated c-Src (Tyr416), c-Src, and GAPDH in NSC-34 cells overexpressing human wild-type or mutant SOD1s treated with various concentrations of dasatinib were measured by western blot. Cells were cultured in serum-free culture medium with doxycycline (Dox, 2 µg/ml), and western blot was performed at 24 h after dasatinib addition.

p27 / p21; 

PubMed: 20145167     


Dasatnib induced cell cycle arrest. Dasatinib induced growth arrest, shown as a cell cycle distribution graph in the lower panel, correlated with increased p27 and p21 levels. Western blotting for levels of p27 and p21 was performed on protein lysates of THP-1 cells treated for 48 hours with indicated doses of dasatinib or DMSO. Detection of actin served as control for comparable protein loading.

p-FAK / p-STAT3; 

PubMed: 23721490     


The effect of dasatinib in cell signalling. Western blot analysis with phosphorylated Src, FAK, Stat3, Akt and MAPK in HCC cell lines after 24 hours treatment of dasatinib. The cell lines were arranged according to their IC50 to dasatinib. The top three were most sensitive, the bottom 3 were least sensitive.

cleaved caspase 3; 

PubMed: 20145167     


Dasatinib induced apoptosis. Dasatinib causes apoptosis in Mo7e-KitD816H cells as detected by cleavage of caspase 3. Whole cell lysates were prepared after 24 hour treatment with dasatinib. Caspase 3 and cleaved capase 3 were analyzed by western blotting. Actin serves as loading control.

23049975 20145167 23721490
Growth inhibition assay
IC50; 

PubMed: 23721490     


9 HCC cell lines were exposed to the dedicated concentrations of dasatinib for 72 hours, and IC50 was tested by MTS. Results represent the mean (± SD) of three experiments.

23721490
Immunofluorescence
SRC / Met; 

PubMed: 26517812     


Immunocytochemistry of SRC and Met localization. Cellular localization of SRC and Met following treatment for 48 h with dasatinib, crizotinib or combination in A. LN-18 and B. U373 cells. Scale bar denotes 10 μm. Nuclei were visualized by DAPI while SRC and Met were labeled with a fluorescein and Texas-red conjugated secondary antibodies, respectively.

F-actin / Actinin-4 / Paxillin; 

PubMed: 31053734     


Conditionally immortalized differentiated podocytes treated for one-hour with 2 µM kinase inhibitor were stained for F-actin (phalloidin), α-actinin-4, paxillin, and nuclei (Hoechst 33342) to assess cytoskeletal and focal adhesion architecture (scale bars = 50 µm). Podocytes treated with dasatinib showed a marked decrease in cell-to-cell contacts, cell size and number of focal adhesions.

α-tubulin; 

PubMed: 26517812     


Combination of dasatinib and crizotinib impedes the formation of the α-tubulin-labeled mitotic spindle. LN-18 cells were treated with dasatinib 0.2 μM, crizotinib 4 μM or their combination for 48 h. Mitotic spindle were visualized using α-tubulin antibody conjugated to a fluorescein-labeled secondary antibody. Nuclei were stained by DAPI. The scale bar denotes 10 μm.

26517812 31053734
ELISA
TNF-α; 

PubMed: 17684099     


U937 cells were differentiated with vitamin D3, pretreated with the indicated concentrations of drugs for 1 h and stimulated with LPS for 6 h. TNF-α secretion was measured by ELISA. The graph shows the mean of two experiments done in duplicate.

E-selectin; 

PubMed: 31110200     


HAoECs were treated with DMSO, a dual FAK/Pyk2 inhibitor (PF-271, 2.5 μM), a Src inhibitor (Dasatinib, 1 μM), or a FAK inhibitor (PF-228, 10 μM) for 1 h prior to TNF-α (10 ng/ml, 6 h) stimulation. Expression levels of E-selectin was determined using ELISA (n = 3, ±SEM).

VCAM-1; 

PubMed: 31110200     


HAoECs were treated with DMSO, a dual FAK/Pyk2 inhibitor (PF-271, 2.5 μM), a Src inhibitor (Dasatinib, 1 μM), or a FAK inhibitor (PF-228, 10 μM) for 1 h prior to TNF-α (10 ng/ml, 6 h) stimulation. Expression levels of VCAM-1 was determined using ELISA (n = 3, ±SEM).

17684099 31110200
In vivo Dasatinib reverses splenomegaly in LMP2A/MYC double transgenic mice. Dasatinib specifically prevents colony formation by LMP2A expressing bone marrow B cells and decreased spleen size in the TgE mice. Spleen mass is significantly decreased among Dasatinib treated Tg6/λ-MYC mice when compared to the control group. Dasatinib inhibits lymphadenopathy in LMP2A/MYC double transgenic mice. Dasatinib reverses splenomegaly in Rag1KO mice engrafted with tumor cells from LMP2A/MYC double transgenic mice. Dasatinib therapy inhibits Lyn phosphorylation in B lymphocyte tumors expressing LMP2A. [3]

Protocol

Kinase Assay:

[1]

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Kinase autophosphorylation assays:

Kinase assays using wild-type and mutant glutathione S-transferase (GST)-Abl fusion proteins (c-Abl amino acids 220-498) are done. GST-Abl fusion proteins are released from glutathione-Sepharose beads before use; the concentration of ATP is 5 μM. Immediately before use in kinase autophosphorylation and in vitro peptide substrate phosphorylation assays, GST-Abl kinase domain fusion proteins are treated with LAR tyrosine phosphatase. After 1-hour incubation at 30 °C, LAR phosphatase is inactivated by addition of sodium vanadate (1 mM). Immunoblot analysis comparing untreated GST-Abl kinase to dephosphorylated GST-Abl kinase is routinely done using phosphotyrosine-specific antibody 4G10 to confirm complete (>95%) dephosphorylation of tyrosine residues and c-Abl antibody CST 2862 to confirm equal loading of GST-Abl kinase. The Dasatinib concentration range is extended to 1,000 nM for mutant T315I. These same inhibitor concentrations are used for the in vitro peptide substrate phosphorylation assays. The three inhibitors are tested over these same concentration ranges against GST-Src kinase and GST-Lyn kinase.
Cell Research:

[1]

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  • Cell lines: Ba/F3 cell lines
  • Concentrations: ~32 nM
  • Incubation Time: 72 hours
  • Method:

    Ba/F3 cell lines are seeded in triplicate and incubated with escalating concentrations of Dasatinib for 72 hours. Proliferation is measured using a methanethiosulfonate-based viability assay. IC50 and IC90 values are reported as the mean of three independent experiments done in quadruplicate. The inhibitor concentration ranges are 0 nM to 32 nM (Dasatinib). The Dasatinib concentration range is extended to 200 nM for mutant T315I.


    (Only for Reference)
Animal Research:

[3]

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  • Animal Models: EμLMP2A (TgE and Tg6 strains), MYC (λ-MYC), and LMP2A/λ-MYC double transgenic mice (Tg6/λ-MYC)
  • Dosages: 30 mg/kg
  • Administration: Administered via i.p.
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 98 mg/mL (200.81 mM)
Water Insoluble
Ethanol Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
4% DMSO+30% PEG 300+5% Tween 80+ddH2O
For best results, use promptly after mixing.
5mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 488.01
Formula

C22H26ClN7O2S

CAS No. 302962-49-8
Storage powder
in solvent
Synonyms BMS-354825
Smiles CC1=C(C(=CC=C1)Cl)NC(=O)C2=CN=C(S2)NC3=CC(=NC(=N3)C)N4CCN(CC4)CCO

In vivo Formulation Calculator (Clear solution)

Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
Dosage mg/kg Average weight of animals g Dosing volume per animal ul Number of animals
Step 2: Enter the in vivo formulation ()
% DMSO % % Tween 80 % ddH2O
CalculateReset

Bio Calculators

Molarity Calculator

Molarity Calculator

Calculate the mass, volume or concentration required for a solution. The Selleck molarity calculator is based on the following equation:

Mass (mg) = Concentration (mM) × Volume (mL) × Molecular Weight (g/mol)

  • Mass
    Concentration
    Volume
    Molecular Weight

*When preparing stock solutions, please always use the batch-specific molecular weight of the product found on the via label and MSDS / COA (available on product pages).

Dilution Calculator

Dilution Calculator

Calculate the dilution required to prepare a stock solution. The Selleck dilution calculator is based on the following equation:

Concentration (start) x Volume (start) = Concentration (final) x Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2 ( Input Output )

  • C1
    V1
    C2
    V2

* When preparing stock solutions always use the batch-specific molecular weight of the product found on the vial label and MSDS / COA (available online).

The Serial Dilution Calculator Equation

  • Serial Dilutions

  • Computed Result

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
Molecular Weight Calculator

Molecular Weight Calculator

Enter the chemical formula of a compound to calculate its molar mass and elemental composition:

Total Molecular Weight: g/mol

Tip: Chemical formula is case sensitive. C10H16N2O2 c10h16n2o2

Instructions to calculate molar mass (molecular weight) of a chemical compound:

To calculate molar mass of a chemical compound, please enter its chemical formula and click 'Calculate'.

Definitions of molecular mass, molecular weight, molar mass and molar weight:

Molecular mass (molecular weight) is the mass of one molecule of a substance and is expressed in the unified atomic mass units (u). (1 u is equal to 1/12 the mass of one atom of carbon-12)
Molar mass (molar weight) is the mass of one mole of a substance and is expressed in g/mol.

Molarity Calculator

Mass Concentration Volume Molecular Weight

Clinical Trial Information

NCT Number Recruitment interventions Conditions Sponsor/Collaborators Start Date Phases
NCT04063124 Recruiting Drug: Dasatinib + Quercetin Alzheimer Disease The University of Texas Health Science Center at San Antonio|Mayo Clinic February 14 2020 Phase 1|Phase 2
NCT04155411 Recruiting Drug: Dasatinib Dasatinib|BCR-ABL|Chronic Myeloid Leukemia Shenzhen Second People''s Hospital December 1 2019 Phase 4
NCT04115059 Recruiting Drug: Dasatinib Waldenstrom Macroglobulinemia|DASATINIB Jorge J. Castillo MD|Bristol-Myers Squibb|Dana-Farber Cancer Institute November 4 2019 Phase 1
NCT03318770 Not yet recruiting Drug: Dasatinib and blinatumomab Acute Lymphoblastic Leukemia Gruppo Italiano Malattie EMatologiche dell''Adulto December 2018 --
NCT03625388 Recruiting Drug: Dasatinib Chronic Myelogenous Leukemia Hikma Pharmaceuticals LLC November 5 2018 Phase 2

Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

Tel: +1-832-582-8158 Ext:3

If you have any other enquiries, please leave a message.

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Frequently Asked Questions

  • Question 1:

    what’s the difference between S1021 and S7782? Which one is better for in vivo studies?

  • Answer:

    Usually, hydrate will be more stable and dissolve better than free base. But this compound (S1021) dissolves better in DMSO than hydrate one (S7782).

  • Question 2:

    Can I give dasatinib to mice by oral gavage? If so, how to dissolve the drug?

  • Answer:

    Our S1021 Dasatinib in 1% DMSO+30% PEG 300+1% Tween 80 at 30 mg/ml is a suspension which you can administrate to mice via oral gavage. If you want a clear solution, it can be dissolved in 4% DMSO+30% PEG 300+5% Tween 80+ddH2O at 5 mg/ml clearly.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID