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.
J Virol. 2020 Feb 14;94(5):e01791-19.
Biochim Biophys Acta. 2017 Jan;1864(1):12-22.
|Source||Biochimica et Biophysica Acta (2017) . Figure 7. Dasatinib was supplied from Abmole Bioscience (Houston, TX, USA).|
|Cell Lines||MDA-MB-231 cells|
|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).|
|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.|
|Incubation time||72 h|
|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|
|Body Surface Area (m2)||0.007||0.025||0.15||0.05||0.02||0.5|
|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 Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for Compound A of 10 mg/kg.
|Solubility||DMSO 68 mg/mL|
 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.
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