Dasatinib-hydrochloride-BMS-354825-hydrochloride-DataSheet-生命科学试剂-MedChemExpress

1、Hotline: 400-820-3792Inhibitors Agonists Screening Librarieswww.MedChemEDasatinib hydrochlorideCat. No.: HY-10181ACAS No.: 854001-07-3Synonyms: BMS 354825 hydrochloride分式: CHClNOS分量: 524.47作靶点: Bcr-Abl; Src; Autophagy作通路: Protein Tyrosine Kinase/RTK; Autophagy储存式: Powder -20C 3 years4C 2 yearsIn sol

2、vent -80C 6 months-20C 1 month溶解性数据体外实验 DMSO : 15 mg/mL (28.60 mM; Need ultrasonic and warming)H2O : 10 mg/mL (19.07 mM; Need ultrasonic)Mass Solvent1 mg 5 mg 10 mg Concentration制备储备液1 mM 1.9067 mL 9.5334 mL 19.0669 mL5 mM 0.3813 mL 1.9067 mL 3.8134 mL10 mM 0.1907 mL 0.9533 mL 1.9067 mL请根据产品在不同溶剂中的溶

3、解度，选择合适的溶剂配制储备液，并请注意储备液的保存式和期限。BIOLOGICAL ACTIVITY物活性 Dasatinib hydrochloride种有效的 AblWT/Src 双重 抑制剂，IC50 值分别为 0.6 nM/0.8 nM；同时抑制 c-KitWT/c-KitD816V，IC50 值分别为 79 nM/37 nM。IC50 & Target IC50: 0.6 nM/0.8 nM (AblWT/Src) 1IC50: 79 nM/37 nM (c-KitWT/c-KitD816V) 21/3 Master of Small Molecules 您边的抑制剂师www.Med

4、ChemE体外研究 Dasatinib potently inhibits wild-type Abl kinase and all mutants except T315I over a narrow range (IC501.7nM). Dasatinib (IC50: 0.8 nM) displays 325-fold greater potency compared with Imatinib against cellsexpressing wild-type Bcr-Abl in Ba/F3 cells 1.体内研究 Daily treatment with Dasatinib (5

5、0 mg/kg) is initiated on day 10. Using this approach, a significant inhibition ofBCPAP orthotopic tumor growth is observed 6 days after treatment (day 16, P=0.014), which is sustainedthrough days 23 and 29 (P=0.0003), compared with vehicle-treated mice 3. Metabolism studies of Dasatinib(50 mg/kg) in

6、 rat suggested that Dasatinib is the major circulating component, whereas multiple metabolitescontributed to the remaining 40-60% of the sample radioactivity at 4 h post dose 4.PROTOCOLKinase Assay 1 Kinase assays using wild-type and mutant glutathione S-transferase (GST)-Abl fusion proteins (c-Abl

7、aminoacids 220-498) are done with minor alterations. GST-Abl fusion proteins are released from glutathione-Sepharose beads before use; the concentration of ATP is 5 M. Immediately before use in kinaseautophosphorylation and in vitro peptide substrate phosphorylation assays, GST-Abl kinase domain fus

8、ionproteins are treated with LAR tyrosine phosphatase. After 1-hour incubation at 30C, LAR phosphatase isinactivated by addition of sodium vanadate (1 mM). Immunoblot analysis comparing untreated GST-Ablkinase to dephosphorylated GST-Abl kinase is routinely done using phosphotyrosine-specific antibo

9、dy 4G10to confirm complete (95%) dephosphorylation of tyrosine residues and c-Abl antibody CST 2862 to confirmequal loading of GST-Abl kinase. The inhibitor concentration ranges for IC50 determinations are 0 to 5,000nM (Imatinib and AMN107) or 0 to 32 nM (Dasatinib). The Dasatinib concentration rang

10、e is extended to1,000 nM for mutant T315I. These same inhibitor concentrations are used for the in vitro peptide substratephosphorylation assays. The three inhibitors are tested over these same concentration ranges against GST-Src kinase and GST-Lyn kinase.MCE has not independently confirmed the acc

11、uracy of these methods. They are for reference only.Cell Assay 1 Ba/F3 cell lines are plated in triplicate and incubated with escalating concentrations of Imatinib, AMN107, orDasatinib for 72 hours. Proliferation is measured using a methanethiosulfonate-based viability assay(CellTiter96 Aqueous One

12、Solution Reagent). IC50 and IC90 values are reported as the mean of threeindependent experiments done in quadruplicate. The inhibitor concentration ranges for IC50 andIC90determinations are 0 to 2,000 nM (Imatinib and AMN107) or 0 to 32 nM (Dasatinib). The imatinibconcentration range is extended to

13、6,400 nM for mutants with IC502,000 nM. The Dasatinib concentrationrange is extended to 200 nM for mutant T315I.MCE has not independently confirmed the accuracy of these methods. They are for reference only.Animal Mice 3Administration 34 Male athymic nude mice (25 grams; 5-week old) are used. Dasati

14、nib (50 mg/kg) is prepared for daily oralgavage (5 d/wk) in 80 mM sodium citrate buffer, pH 3.0. For the orthotopic murine model, mice arerandomized on day 10 based on bioluminescence activity to receive drug or vehicle. In the metastatic murinemodel, mice receives dasatinib or vehicle, as described

15、 earlier, starting 2 days before intracardiac injection(pretreatment), or on day 11 following randomization (posttreatment).Rats 42/3 Master of Small Molecules 您边的抑制剂师www.MedChemEDasatinib is dosed to male Wistar-Han (WH) rats at 50 mg/kg orally in 0.5% methylcellulose. The automatedrat blood collec

16、tion device is programmed to collect 200 L of blood at predetermined intervals. At each timepoint, the accusampler is programmed to directly spot 20 L of blood twice (two spots) onto the DBS card.The remaining 160 L of liquid blood is collected into sodium EDTA-containing tubes. Plasma samples areob

17、tained after immediate centrifugation of blood at 11,000 rpm for 5 min. The plasma samples are stored at80C until analyses. The DBS samples are dried under room temperature for a minimum of 2 h and storedin a plastic bag in the dessicator until sample analysis.MCE has not independently confirmed the

18、 accuracy of these methods. They are for reference only.户使本产品发表的科研献 Sci Transl Med. 2018 Jul 18;10(450). pii: eaaq1093. J Pineal Res. 2019 May 28:e12588. J Clin Invest. 2019 Mar 1;129(3):972-987. Leukemia. 2012 Oct;26(10):2233-44. J Hematol Oncol. 2018 Aug 29;11(1):109.See more customer validations

19、on HYPERLINK / www.MedChemEREFERENCES1. OHare T, et al. In vitro activity of Bcr-Abl inhibitors AMN107 and BMS-354825 against clinically relevant imatinib-resistant Abl kinasedomain 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