Dasatinib

製品コードS1021 バッチS102108

印刷

化学情報

Chemical Structure Synonyms BMS-354825 Storage
(From the date of receipt)		 3 years -20°C powder
1 years -80°C in solvent
化学式

C22H26ClN7O2S
分子量 488.01 CAS No. 302962-49-8
Solubility (25°C)* 体外 DMSO 98 mg/mL (200.81 mM)
Water Insoluble
Ethanol Insoluble
体内 （毎回新しく調製した物を用意してください）
Homogeneous suspension
CMC-NA
≥5mg/ml Taking the 1 mL working solution as an example, add 5 mg of this product to 1 ml of CMC-Na solution, mix evenly to obtain a homogeneous suspension with a final concentration of 5 mg/ml.
Clear solution
4%DMSO 30%PEG300 5%Tween80 61%ddH2O

この製剤はselleckのラボで検証済みです。上記の溶解方法がご要望を満たさない場合、selleckの営業担当までお問い合わせ頂ければ、個別の試験を行います。

 5.000mg/ml (10.25mM) Taking the 1 mL working solution as an example, add 40 μL of 125 mg/ml clarified DMSO stock solution to 300 μL of PEG300, mix evenly to clarify it; add 50 μL of Tween80 to the above system, mix evenly to clarify it; then continue to add 610 μL of ddH2O to adjust the volume to 1 mL. The mixed solution should be used immediately for optimal results. 
* <1 mg/ml means slightly soluble or insoluble.
* 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.

溶剤液（一定の濃度）を調合する

生物活性

製品説明 Dasatinibは新規の強力なマルチターゲット阻害剤であり、cell-free assy における Abl, Src および c-Kit に対する IC50 はそれぞれ < 1 nM, 0.8 nM および 79 nM です。Dsatinib はオートファジー (autophagy) とアポトーシス (apoptosis) を誘発し、抗腫瘍活性を示します。
in vitro

Dasatinib is more effective in inhibiting the proliferation of Ba/F3 cells expressing wild-type Bcr-Abl and Bcr-Abl mutants, with the exception of T315I. This compound has a two-log (∼325-fold) increased potency. It potently inhibits wild-type Abl kinase and all mutants except T315I over a narrow range. This agent directly targets wild-type and mutant Abl kinase domains and inhibits autophosphorylation and substrate phosphorylation in a concentration-dependent manner. It displays 325-fold greater potency 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 this compound treated wells. In the presence of this chemical, 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 this agent. [3] Its 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 this compound (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 this chemical 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]
in vivo

Dasatinib reverses splenomegaly in LMP2A/MYC double transgenic mice. This compound 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 this compound treated Tg6/λ-MYC mice when compared to the control group. It inhibits lymphadenopathy in LMP2A/MYC double transgenic mice. This chemical reverses splenomegaly in Rag1KO mice engrafted with tumor cells from LMP2A/MYC double transgenic mice. Its therapy inhibits Lyn phosphorylation in B lymphocyte tumors expressing LMP2A. [3]

プロトコル(参考用のみ)

キナーゼアッセイ 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.
細胞アッセイ 細胞株 Ba/F3 cell lines
濃度 ~32 nM
反応時間 72 hours
実験の流れ

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 (this compound). The concentration range of this chemical is extended to 200 nM for mutant T315I.
動物実験 動物モデル EμLMP2A (TgE and Tg6 strains), MYC (λ-MYC), and LMP2A/λ-MYC double transgenic mice (Tg6/λ-MYC)
投薬量 30 mg/kg
投与方法 Administered via i.p.

参考

  • https://pubmed.ncbi.nlm.nih.gov/15930265/
  • https://pubmed.ncbi.nlm.nih.gov/16434489/
  • https://pubmed.ncbi.nlm.nih.gov/22609829/
  • https://pubmed.ncbi.nlm.nih.gov/22586301/

カスタマーフィードバック

Data from [Cell Res, 2011, 21, 1080-1087]

Data from [Clin Cancer Res, 2011, 17, 762-770]

Data from [Clin Cancer Res, 2011, 17, 762-770]

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長期の保管のために-20°Cの下で製品を保ってください。

人間や獣医の診断であるか治療的な使用のためにでない。

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