Biological Activity

Dasatinib (BMS-354825) is a small molecule inhibitor of both the SRC and BCR/ABL tyrosine kinases, with IC50's for the isolated kinases of 0.55 and 3.0 nM, respectively. Dasatinib also inhibits Lyn (IC50 = 8.5 nM) and Src (IC50 = 3.0 nM) kinase activities in vitro using 0.1 mg/mL poly (Glu4-Tyr) as the substrate. Dasatinib has greater potency than imatinib mesylate and has activity against the majority of kinase mutations in imatinib-resistant chronic myeloid leukemia.

Product Citations

• 

  Nat Commun. 2023 Nov 27;14(1):7783.

  Local H2 release remodels senescence microenvironment for improved repair of injured bone
  Dasatinib purchased from AbMole

• 

  J Virol. 2020 Feb 14;94(5):e01791-19.

  Targeting Kaposi's Sarcoma-Associated Herpesvirus ORF21 Tyrosine Kinase and Viral Lytic Reactivation by Tyrosine Kinase Inhibitors Approved for Clinical Use
  Dasatinib purchased from AbMole

• 

  Biochim Biophys Acta. 2017 Jan;1864(1):12-22.

  Involvement of caveolin-1 in low shear stress-induced breast cancer cell motility and adhesion: Roles of FAK/Src and ROCK/p-MLC pathways.
  Dasatinib purchased from AbMole

Customer Product Validations & Biological Datas

	Source	Biochimica et Biophysica Acta (2017) . Figure 7. Dasatinib was supplied from Abmole Bioscience (Houston, TX, USA).
	Method	Flow cytometry
	Cell Lines	MDA-MB-231 cells
	Concentrations	20 μM
	Incubation Time	24 h
	Results	Apoptosis analysis by flow cytometry showed that shCtrl- and shCav-1-transfected MDA-MB-231 cells treated with Dasatinib for 24 h maintained high cell viability (N80%), with no disparity in apoptosis (Fig. 7B).

Protocol (for reference only)

Cell Experiment
Cell lines	Ba/F3 cell lines
Preparation method	Cellular proliferation assays. Ba/F3 cell lines were plated in triplicate and incubated with escalating concentrations of imatinib, AMN107, or BMS-354825 for 72 hours. Proliferation was measured using a methanethiosulfonate-based viability assay (CellTiter96 Aqueous One Solution Reagent; Promega). IC50 and IC90 values are reported as the mean of three independent experiments done in quadruplicate. The inhibitor concentration ranges for IC50 and IC90 determinations were 0 to 2,000 nmol/L (imatinib and AMN107) or 0 to 32 nmol/L (BMS-354825). The imatinib concentration range was extended to 6,400 nmol/L for mutants with IC50 >2,000 nmol/L. The BMS-354825 concentration range was extended to 200 nmol/L for mutant T315I.
Concentrations	0~2000nM
Incubation time	72 h

Animal Experiment
Animal models	primary human Ph+ B-ALL xenografts
Formulation	dissolved in a mixture of polypropylene glycol (Sigma-Aldrich) diluted in water (50:50)
Dosages	5 mg/kg/day for two weeks
Administration	oral gavage

Chemical Information

Molecular Weight	488.01
Formula	C22H26ClN7O2S
CAS Number	302962-49-8
Solubility (25°C)	DMSO 68 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

Conversion of different model animals based on BSA (PMID: 27057123)

Species	Mouse	Rat	Rabbit	Guinea pig	Hamster	Dog
Weight (kg)	0.02	0.15	1.8	0.4	0.08	10
Body Surface Area (m2)	0.007	0.025	0.15	0.05	0.02	0.5
Km factor	3	6	12	8	5	20

Animal A (mg/kg) = Animal B (mg/kg) multiplied by	Animal B Km
	Animal A Km

For example, to modify the dose of Compound A used for a mouse (20 mg/kg) to a dose based on the BSA for a rat, multiply 20 mg/kg by the K_m factor for a mouse and then divide by the K_m factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.

References

[1] Sano et al. Intern Med. Pulmonary arterial hypertension caused by treatment with dasatinib for chronic myeloid leukemia critical alert.

[2] Yang et al. Blood. Anti-tumor T cell responses contribute to the effects of dasatinib on c-KIT mutant murine mastocytoma and are potentiated by anti-OX40.

[3] Radich et al. Blood. A randomized trial of dasatinib 100 mg vs imatinib 400 mg in newly diagnosed chronic phase chromic myeloid leukemia.

[4] Sharma et al. Asia Pac J Clin Oncol. Dasatinib in chronic myeloid leukemia: A limited Indian experience.

[5] Agarwal et al. Mol Cancer Ther. Active efflux of dasatinib from the brain limits efficacy against murine glioblastoma: broad implications for the clinical use of molecularly-targeted agents.

[6] Birch et al. Biomed Chromatogr. Simple methodology for the therapeutic drug monitoring of the tyrosine kinase inhibitors dasatinib and imatinib.

[7] Noy et al. Leuk Res. Dasatinib inhibits leukaemic cell survival by decreasing PRH/Hhex phosphorylation resulting in increased repression of VEGF signalling genes.

[8] Kralj et al. J Chromatogr B Analyt Technol Biomed Life Sci. Simultaneous measurement of imatinib, nilotinib and dasatinib in dried blood spot by ultra high performance liquid chromatography tandem mass spectrometry.

[9] Kuckertz et al. Onkologie. Comparison of the effects of two kinase inhibitors, sorafenib and dasatinib, on chronic lymphocytic leukemia cells.