Dasatinib (BMS-354825)

製品コード:S1021

For research use only.

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.

Dasatinib (BMS-354825)化学構造

CAS No. 302962-49-8

サイズ 価格(税別)
10mM (1mL in DMSO) JPY 25200
JPY 26400
JPY 63400
JPY 119700

代表番号: 03-5615-9297|電子メール:[email protected]
よく尋ねられる質問

文献中Selleckの製品使用例(470)

製品安全説明書

Src阻害剤の選択性比較

相関Src製品

生物活性

製品説明 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.
ターゲット
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
体外試験

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]

細胞データ
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
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アッセイ
Methods Test Index PMID
Western blot phospho-c-Abl(Tyr245) / phospho-c-Src(Tyr416) ; p27 / p21 ; p-FAK / p-STAT3 ; cleaved caspase 3 23049975 20145167 23721490
Growth inhibition assay IC50 23721490
Immunofluorescence SRC / Met ; F-actin / Actinin-4 / Paxillin ; α-tubulin 26517812 31053734
ELISA TNF-α ; E-selectin ; VCAM-1 17684099 31110200
体内試験 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]

お薦めの試験操作(参考用のみ)

キナーゼ試験:

[1]

  • 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.

細胞試験:

[1]

  • 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 (Dasatinib). The Dasatinib concentration range is extended to 200 nM for mutant T315I.

動物試験:

[3]

  • 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.

溶解度 (25°C)

体外

体内

左から(NMPから)右の順に溶剤を製品に加えます(文献ではなく、Selleckの実験によるデータ):
4% DMSO+30% PEG 300+5% Tween 80+ddH2O
混合させたのち直ちに使用することを推奨します。

5mg/mL

化学情報

分子量 488.01
化学式

C22H26ClN7O2S

CAS No. 302962-49-8
Storage 3年 -20°C
2年 -80°C in solvent
Smiles CC1=C(C(=CC=C1)Cl)NC(=O)C2=CN=C(S2)NC3=CC(=NC(=N3)C)N4CCN(CC4)CCO

投与溶液組成計算機(クリア溶液)

ステップ1:実験データを入力してください。(実験操作によるロスを考慮し、動物数を1匹分多くして計算・調製することを推奨します)

mg/kg g μL

ステップ2:投与溶媒の組成を入力してください。(ロット毎に適した溶解組成が異なる場合があります。詳細については弊社までお問い合わせください)

% DMSO % % Tween 80 % ddH2O
%DMSO %

計算結果:

投与溶媒濃度: mg/ml;

DMSOストック溶液調製方法: mg 試薬を μL DMSOに溶解する(濃度 mg/mL, 注:濃度が当該ロットのDMSO溶解度を超える場合はご連絡ください。 )

投与溶媒調製方法:Take μL DMSOストック溶液に μL PEG300,を加え、完全溶解後μL Tween 80,を加えて完全溶解させた後 μL ddH2O,を加え完全に溶解させます。

投与溶媒調製方法:μL DMSOストック溶液に μL Corn oil,を加え、完全溶解。

注意:1.ストック溶液に沈殿、混濁などがないことをご確認ください;
2.順番通りに溶剤を加えてください。次のステップに進む前に溶液に沈殿、混濁などがないことを確認してから加えてください。ボルテックス、ソニケーション、水浴加熱など物理的な方法で溶解を早めることは可能です。

便利ツール

質量 濃度 体積 分子量

臨床試験

NCT Number Recruitment Interventions Conditions Sponsor/Collaborators Start Date Phases
NCT05198843 Recruiting Drug: Dasatinib|Dietary Supplement: Icosapent Ethyl Anatomic Stage IV Breast Cancer AJCC v8|Metastatic Triple-Negative Breast Inflammatory Carcinoma National Cancer Institute (NCI) March 25 2022 Phase 1|Phase 2
NCT04925648 Recruiting Drug: Dasatinib|Drug: Darolutamide Metastatic Prostate Cancer St Vincent''s Hospital Sydney October 18 2021 Phase 2
NCT04933526 Recruiting Drug: Flumatinib|Drug: Dasatinib Chronic Myeloid Leukemia in Chronic Phase Shenzhen Second People''s Hospital July 1 2021 Phase 4
NCT05433896 Completed Drug: Dasatinib ASD|Drug: Omeprazole 40 MG Pharmacokinetics|Drug Interactions Xspray Pharma AB|Axis Clinicals Limited November 1 2020 Phase 1

(data from https://clinicaltrials.gov, updated on 2022-08-01)

技術サポート

ストックの作り方、阻害剤の保管方法、細胞実験や動物実験の際に注意すべき点など、製品を取扱う時に問い合わせが多かった質問に対しては取扱説明書でお答えしています。

Handling Instructions

他に質問がある場合は、お気軽にお問い合わせください。

* 必須

大学・企業名を記入してください
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よくある質問(FAQ)

質問1:
what’s the difference between S1021 and S7782? Which one is better for in vivo studies?

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

質問2:
Can I give dasatinib to mice by oral gavage? If so, how to dissolve the drug?

回答
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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