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受注：045-509-1970 |
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化学情報
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Synonyms | BMS-354825 Monohydrate | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
| 化学式 | C22H28ClN7O3S |
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| 分子量 | 506.02 | CAS No. | 863127-77-9 | |
| Solubility (25°C)* | 体外 | DMSO | 100 mg/mL warmed with 50ºC water bath (197.62 mM) | |
| Water | Insoluble | |||
| Ethanol | Insoluble | |||
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* <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. |
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溶剤液（一定の濃度）を調合する
生物活性
| 製品説明 | Dasatinib Monohydrate (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, respectively. |
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| in vitro | 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] |
| in vivo | 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] |
プロトコル(参考用のみ)
| キナーゼアッセイ | Kinase autophosphorylation assays | |
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| 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 (Dasatinib). The Dasatinib concentration range is extended to 200 nM for mutant T315I. |
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| 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
カスタマーフィードバック
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Data from [Cell Res, 2011, 21, 1080-1087]
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Data from [Clin Cancer Res, 2011, 17, 762-770]
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Data from [Clin Cancer Res, 2011, 17, 762-770]
Selleckの高級品が、幾つかの出版された研究調査結果（以下を含む）で使われた：
| SMYD5 is a novel epigenetic gatekeeper of the mild hypothermia response [ bioRxiv, 2023, 2023.05.11.540170] | PubMed: 37333301 |
| THY1-mediated mechanisms converge to drive YAP activation in skin homeostasis and repair [ Nat Cell Biol, 2022, 24(7):1049-1063] | PubMed: 35798842 |
| MicroRNA-485-5p targets keratin 17 to regulate oral cancer stemness and chemoresistance via the integrin/FAK/Src/ERK/β-catenin pathway [ J Biomed Sci, 2022, 29(1):42] | PubMed: 35706019 |
| The interactions between integrin α5β1 of liver cancer cells and fibronectin of fibroblasts promote tumor growth and angiogenesis [ Int J Biol Sci, 2022, 18(13):5019-5037] | PubMed: 35982891 |
| GSK3 inhibition circumvents and overcomes acquired lorlatinib resistance in ALK-rearranged non-small-cell lung cancer [ NPJ Precis Oncol, 2022, 6(1):16] | PubMed: 35301419 |
| Proteome-Wide Deconvolution of Drug Targets and Binding Sites by Lysine Reactivity Profiling [ Anal Chem, 2022, 10.1021/acs.analchem.1c05455] | PubMed: 35147412 |
| Induction of IDO1 and Kynurenine by Serine Proteases Subtilisin, Prostate Specific Antigen, CD26 and HtrA: A New Form of Immunosuppression [ Front Immunol, 2022, 13:841045] | PubMed: 35251038 |
| In Vitro Validation of the Therapeutic Potential of Dendrimer-Based Nanoformulations against Tumor Stem Cells [ Int J Mol Sci, 2022, 23(10)5691] | PubMed: 35628503 |
| Mcl-1 inhibition overcomes BET inhibitor resistance induced by low FBW7 expression in breast cancer [ J Cell Mol Med, 2022, 10.1111/jcmm.17210] | PubMed: 35132755 |
| Establishment and Characterization of NCC-PMP1-C1: A Novel Patient-Derived Cell Line of Metastatic Pseudomyxoma Peritonei [ J Pers Med, 2022, 12(2)258] | PubMed: 35207746 |
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。
各々の製品のための特定の保管と取扱い情報は、製品データシートの上で示されます。大部分のSelleck製品は、推薦された状況の下で安定です。製品は、推薦された保管温度と異なる温度で、時々出荷されます。長期の保管のために必要とされてそれと異なる温度で、多くの製品は、短期もので安定です。品質を維持するが、夜通しの積荷のために最も経済的な貯蔵状況を用いてあなたの送料を保存する状況の下に、製品が出荷されることを、我々は確実とします。製品の受領と同時に、製品データシートの上で貯蔵推薦に従ってください。