Dasatinib Monohydrate

製品コードS7782 別名:BMS-354825 Monohydrate

Dasatinib Monohydrate化学構造

分子量(MW):506.02

Dasatinib Monohydrate 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, respectively.

サイズ 価格(税別)  
JPY 16102.00
JPY 32702.00

文献中Selleckの製品使用例(58)

カスタマーフィードバック(11)

  • Nature, 2016, 534(7607):341-6.. Dasatinib Monohydrate purchased from Selleck.

    Combinational treatment of kinase inhibitors induces the similar phenotype produced by PP1. All images are lateral view with dorsal to the top and anterior to the left. The combinational treatment of Dasatinib (D) or U0126 (U) with Sunitinib (SU),PTK787 (PTK), or ZM323881 (Z) resulted in the shrinkage of dorsal aorta.

    Cell Res 2011 21, 1080-1087. Dasatinib Monohydrate purchased from Selleck.

  • Cytotoxicity by Dasatinib and Nutlin-3 used alone or in combination in B-CLL patient leukemic cells. B-CLL patient leukemic cells were exposed to serial doses of Dasatinib or Nutlin- 3 used either alone or in combination, with a fixed ratio, for 48 hours. Dose-effect plots, to determine drug efficacy, are shown for representative B-CLL samples, including 3 patients carrying 17p- (Pt. #7, Pt. #8, and Pt. #10). The decrease of cell viability, labeled "effect" on the Y-axis, was determined in assays done at least twice in duplicate.

    Clin Cancer Res 2011 17, 762-770. Dasatinib Monohydrate purchased from Selleck.

    Dasatinib interferes with the p53 transcriptional activity induced by Nutlin-3. Leukemic cell lines were exposed for 24 hours to Dasatinib (10 μM) and Nutlin-3 (10 μM), used either alone or in combination, as indicated. Levels of p53 (A), MDM2 and p21 (B) were assessed by Western blot analysis of total cell lysates. Representative examples of Western blot results are shown. Tubulin staining is shown as loading control; after densitometric analyses, p53 as well as MDM2 and p21 protein levels are expressed as folds of protein modulation, by the indicated treatments, with respect to the control untreated cultures set to 1 (hatched line). *P < 0.05 with respect to the Nutlin-3-treated cultures.

     

     

    Clin Cancer Res 2011 17, 762-770. Dasatinib Monohydrate purchased from Selleck.

  • Role of Akt in Dasatinib cytotoxicity and in DasatinibtNutlin-3 synergy. A, whole cell lysates were prepared from EHEB and BJAB cell lines treated (for 16 hours) as indicated, and hybridized with a human Phospho-Kinase array kit. Spot densities of phospho-proteins were quantified using Image Quant TL software and normalized to those of positive controls (set at 100) on the same membrane. The analysis of modulation of phosphorylation signals for P-ERK1/2, P-p38, and P-Akt are reported (*P < 0.05). Validation of phospho-kinase array results was carried out by Western blot analysis of P-Akt levels.

     

     

    Clin Cancer Res 2011 17, 762-770. Dasatinib Monohydrate purchased from Selleck.

    Impact of the TKI erlotinib, lapatinib, dasatinib, and sorafenib on the viability of MDS/AML cells. MOLM-13 (A) and HL-60 (B) cells were incubated with the indicated doses (given in mM below the x-axis) of the 4 TKI, and cellular viability was assessed by MTT assay after 24, 48 and 72 h of incubation. Changes in viability are given as percentage of cells as compared to non-treated control samples. This experiment was repeated at least three times, yielding comparable results. Graphs show representative results of one experiment carried out in duplicates (mean standard deviation).

     

     

    Biochem Pharmacol 2011 82, 1457-1466. Dasatinib Monohydrate purchased from Selleck.

  • Capacity of the TKI to overcome the AML-typical differentiation blockage. The myeloid cell lines MOLM-13 and HL-60 were incubated for 6 days with 0.01% DMSO (serving as a negative solvent control), 1 μM of ATRA (serving as a positive control), as well as with the indicated doses of the four TKI. (A) Representative May -Gruenwald -Giemsa staining of MOLM-13 cells, (B) quantitation of the percentage of MOLM-13 cells exhibiting at least two morphological signs of differentiation (that is a decrease in cytoplasmic basophilia, a reduction of the nucleo-cytoplasmic ratio, appearance of nuclear lobulation and/or cytoplasmic granules). Percentages were evaluated by examining at least 100 cells/condition; (C) representative FACS overlays of MOLM-13 cells depicting TKI-induced CD11b expression (black line) as compared to the isotype (shaded grey); (D) quantitation of TKI-induced CD11b-expression in MOLM-13 cells; (E) representative slides depicting morphology/staining of MOLM-13 cells assessed in the NBT-reduction assay; (F) respective quantitative assessment demonstrating the NBT-reducing capacity under the different drugs; (G) representative May-Gruenwald-Giemsa staining of HL-60 cells.

     

     

    Biochem Pharmacol 2011 82, 1457-1466. Dasatinib Monohydrate purchased from Selleck.

    Cytotoxicity by Dasatinib treatment in leukemic cells.Leukemic cell lines were exposed to Dasatinib (10 μM). Upon treatment, cell viability (a) was calculated as percentage with respect to the control vehicle cultures (set to 100% for each cell line) and induction of apoptosis (b) was calculated as percentage of Annexin V+/PI+ cells after 48 h of treatment.

     

     

    Invest New Drugs 2010 30, 417-422. Dasatinib Monohydrate purchased from Selleck.

  • Human phospho-kinase array analysis in response to Dasatinib treatment. Whole cell lysates were prepared from EHEB (p53wt) and BJAB (p53mut) B cell lines, either left untreated or exposed to Dasatinib for 24 h, and hybridized with a human Phospho-Kinase array kit. Spot densities of phospho-proteins were quantified using Image Quant TL software and normalized to those of positive controls on the same membrane. In a, intense decreases of signal of P-p38, PERK1/2 and P-CREB in response to Dasatinib are indicated by arrows in the membranes, and intensity of corresponding spots are reported as graphics. In b, analysis of modulation of phosphorylation of STAT family members in response to Dasatinib (spots not shown). The means±SD of three independent experiments are shown. Asterisk indicates P<0.05 against untreated.

    Invest New Drugs 2010 30, 417-422. Dasatinib Monohydrate purchased from Selleck.

    Cells were either left untreated (Unt.) or exposed to Dasatinib (Das.) for 24 h. Equal amounts of cell lysates were analyzed for ERK1/2, p38 and CREB phosphorylation by Western blot using antibodies specific for the native form of the kinases and for residues that are phosphorylated (P-) in each kinase upon activation. One of three experimentswith similar results is shown. Protein bands were quantified by densitometry and level of PERK1/2, P-p38 and P-CREB expressed as arbitrary units,were calculated for each cell line after normalization to total ERK1/2, p38 and CREB respectively

     

     

    Invest New Drugs 2010 30, 417-422. Dasatinib Monohydrate purchased from Selleck.

  • Cell vability test result. Different cell lines (A2C12, Beta D5, Gamma A3, Gamma D12, A549, CaCo2,Hep G2) were treated with different concentration of Dasatinib.

     

     

    Dr. Thomas Kruwel of Fraunhofer-Institute for Toxicology and Experimental Medicine-Dasatinib (BMS-354825) purchased from Selleck. Dasatinib Monohydrate purchased from Selleck.

製品安全説明書

Src阻害剤の選択性比較

生物活性

製品説明 Dasatinib Monohydrate 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, respectively.
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]

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]

+ 展開

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]

+ 展開
  • 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.


    (参考用のみ)
動物試験:

[3]

+ 展開
  • 動物モデル: EμLMP2A (TgE and Tg6 strains), MYC (λ-MYC), and LMP2A/λ-MYC double transgenic mice (Tg6/λ-MYC)
  • 製剤: DMSO
  • 投薬量: 30 mg/kg
  • 投与方法: Administered via i.p.
    (参考用のみ)

溶解度 (25°C)

体外 DMSO 21 mg/mL (41.5 mM) warming
Water Insoluble
Ethanol Insoluble
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):
2% DMSO+30% PEG 300+dd H2O
混合させたのち直ちに使用することを推奨します。
5mg/mL

* 溶解度測定はSelleck技術部門によって行われており、その他文献に示されている溶解度と差異がある可能性がありますが、同一ロットの生産工程で起きる正常な現象ですからご安心ください。

化学情報

分子量 506.02
化学式

C22H28ClN7O3S

CAS No. 863127-77-9
保管
in solvent
別名 BMS-354825 Monohydrate

便利ツール

モル濃度計算器

モル濃度計算器

求めたい質量、体積または濃度を計算してください。

質量 (g) = 濃度 (mol/L) x 体積 (L) x 分子量 (g/mol)

モル濃度計算器方程式

  • 質量
    濃度
    体積
    分子量

*貯蔵液を準備するとき、常に、オンであるとわかる製品のバッチに特有の分子量を使って、を通してラベルとMSDS/COA(製品ページで利用可能な)。

希釈計算器

希釈計算器

貯蔵液を準備するために必要な希釈率を計算してください。Selleck希釈計算器は、以下の方程式に基づきます:

開始濃度 x 開始体積 = 最終濃度 x 最終体積

希釈の計算式

この方程式は、一般に略語を使われます:C1V1 = C2V2 ( 入力 出力 )

  • C1
    V1
    C2
    V2

常に貯蔵液を準備するとき、小びんラベルとMSDS/COA(オンラインで利用できる)で見つかる製品のバッチに特有の分子量を使ってください。

連続希釈計算器方程式

  • 連続希釈剤

  • 計算結果

  • C1=C0/X C1: LOG(C1):
    C2=C1/X C2: LOG(C2):
    C3=C2/X C3: LOG(C3):
    C4=C3/X C4: LOG(C4):
    C5=C4/X C5: LOG(C5):
    C6=C5/X C6: LOG(C6):
    C7=C6/X C7: LOG(C7):
    C8=C7/X C8: LOG(C8):
分子量計算器

分子量计算器

そのモル質量と元素組成を計算するために、合成物の化学式を入力してください:

総分子量:g/mol

チップス: 化学式は大文字と小文字の区別ができます。C10H16N2O2 c10h16n2o2

モル濃度計算器

質量 濃度 体積 分子量

臨床試験

NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT03885830 Not yet recruiting CML Chronic Phase|CML (Chronic Myelogenous Leukemia|CML - Philadelphia Chromosome|Chronic Myeloid Leukemia|Chronic Myeloid Leukemia Chronic Phase UNC Lineberger Comprehensive Cancer Center May 2019 --
NCT03885830 Not yet recruiting CML Chronic Phase|CML (Chronic Myelogenous Leukemia|CML - Philadelphia Chromosome|Chronic Myeloid Leukemia|Chronic Myeloid Leukemia Chronic Phase UNC Lineberger Comprehensive Cancer Center May 2019 --
NCT03878524 Not yet recruiting Breast Cancer|Prostate Cancer|Pancreatic Cancer|Acute Myelogenous Leukemia OHSU Knight Cancer Institute|Oregon Health and Science University|Prospect Creek Foundation March 14 2019 Phase 1
NCT03878524 Not yet recruiting Breast Cancer|Prostate Cancer|Pancreatic Cancer|Acute Myelogenous Leukemia OHSU Knight Cancer Institute|Oregon Health and Science University|Prospect Creek Foundation March 14 2019 Phase 1
NCT03318770 Not yet recruiting Acute Lymphoblastic Leukemia Gruppo Italiano Malattie EMatologiche dell''Adulto December 2018 --
NCT03318770 Not yet recruiting Acute Lymphoblastic Leukemia Gruppo Italiano Malattie EMatologiche dell''Adulto December 2018 --

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

よくある質問(FAQ)

  • 質問1:

    What’s the difference between S1021 and S7782?

  • 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).

Srcシグナル伝達経路

相関Src製品

Tags: Dasatinib Monohydrateを買う | Dasatinib Monohydrate ic50 | Dasatinib Monohydrate供給者 | Dasatinib Monohydrateを購入する | Dasatinib Monohydrate費用 | Dasatinib Monohydrate生産者 | オーダーDasatinib Monohydrate | Dasatinib Monohydrate化学構造 | Dasatinib Monohydrate分子量 | Dasatinib Monohydrate代理店
×

大阪市内で「G20サミット」が開催されることに伴い、大阪府内で大規模な交通規制が行われる影響で、6月26日(水)から7月1日(月)までの間、下記地域へ出荷が行えなくなります。
対象地域
大阪府(全域)、兵庫県(芦屋市、尼崎市、伊丹市、西宮市)
上記地域より西の地域につきましては納期の遅延が予想されます。
また、国際便も遅延が予想されているため国内在庫がない製品の納期が一週間程度遅れる可能性がございます。
ご不便をおかけいたしますが、宜しくお願い申し上げます。

×
細胞株 試験類型 濃度 培養時間 溶剤類型 活性叙述 PMID