Entospletinib (GS-9973)

製品コードS7523 バッチS752304

印刷

化学情報

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

C23H21N7O
分子量 411.46 CAS No. 1229208-44-9
Solubility (25°C)* 体外 DMSO (warmed with 50ºC water bath) 27 mg/mL (65.61 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。

 2.500mg/ml (6.08mM) Taking the 1 mL working solution as an example, add 40 μL of clarified DMSO stock solution of 62.5 mg/ml 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 make it clear. Volume up 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 Entospletinib (GS-9973) is an orally bioavailable, selective Syk inhibitor with IC50 of 7.7 nM in a cell-free assay and showed 13- to >1000-fold cellular selectivity for Syk over other kinases(including Jak2, ckit, Flt3, Ret, KDR) as assessed by target protein phosphorylation or functional response.
in vitro

Entospletinib (GS-9973) shows good bidirectional permeability across Caco-2 cell monolayers in vitro. In cells, it also shows excellent selectivity for Syk, and potently inhibits BCR-mediated activation and proliferation of B-cells as well as immune-complex-stimulated cytokine production in monocytes. [1] The combination of this compound synergistically inhibits CLL cell viability and further disrupts chemokine signaling. [2]
in vivo

Entospletinib (GS-9973) (1 mg/kg p.o.) shows moderate to high bioavailability in rat and dog. In a rat collagen-induced arthritis model, it (1-10 mg/kg p.o.) significantly inhibits ankle inflammation. Moreover, this compound also shows disease-modifying activity in multiple histological measurements, including inhibition of pannus formation, cartilage damage, bone resorption, and peritosteal bone formation with ED50 ranging from 1.2 to 3.9 mg/kg . [1]
特徴 Orally bioavailable Syk-selective inhibitor that has been tested in Phase II clinical trials for treatment of Haematological Malignancies.

プロトコル(参考用のみ)

キナーゼアッセイ Kinase Assays
Full-length baculovirus-expressed Syk kinase activity is measured in a Lance-based assay format in a final volume of 25 μL containing 25 mM Tris–HCl, pH 7.5, 5 mM β-glycerophosphate, 2 mM DTT, 0.1 mM Na3VO4, 10 mM MgCl2, 0.5 μM Promega PTK biotinylated peptide substrate 1, 0.01% casein, 0.01% Triton X-100, and 40 mM ATP (Km for ATP) incubated at room temperature for 60 min. Reactions are stopped with the addition of 30 mM EDTA containing 30 μL of SA-APC and 4 nM PT-66 antibody and the plates measured on a Perkin-Elmer Envision. IC50 values for Entospletinib (GS-9973) are determined using a four-parameter linear regression algorithm.
細胞アッセイ 細胞株 MV-4-11 cells
濃度 ~10 μM
反応時間 72 hours
実験の流れ

Functional impact on cellular Flt3 activity is determined by measuring the inhibition of MV-4-11 cell proliferation by Entospletinib (GS-9973). A total of 104 cells are diluted in RPMI medium containing 10% FBS in 96-well flat-bottomed tissue culture plates and incubated with compound dilutions for 72 h at 37 癈. Alamar blue (10%) is added to the cells, which were incubated for an additional 12-18 h at 37 癈, and inhibition of the relative cell numbers is determined by spectrophotometer readings at 570/600 nm.
動物実験 動物モデル Rat Collagen-Induced Arthritis (CIA) Model
投薬量 ~10 mg/kg bid
投与方法 p.o.

参考

  • https://pubmed.ncbi.nlm.nih.gov/24779514/
  • https://pubmed.ncbi.nlm.nih.gov/24659719/

カスタマーフィードバック

Data from [Data independently produced by , , Blood, 2016, 127(25):3192-201]

Data from [Data independently produced by , , J Hematol Oncol, 2018, 11(1):23]

Data from [Data independently produced by , , Biochim Biophys Acta, 2017, 1864(4):687-696]

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：

Loss of NF1 in Melanoma Confers Sensitivity to SYK Kinase Inhibition [ Cancer Res, 2023, 83(2):316-331] PubMed: 36409827
The selective inhibition of the Syk tyrosine kinase ameliorates experimental autoimmune arthritis [ Front Immunol, 2023, 14:1279155] PubMed: 38111569
Bacterial DNA promoting inflammation via the Sgk1/Nedd4L/Syk pathway in mast cells contributes to antihistamine non-responsive CSU [ J Leukoc Biol, 2023, qiad025] PubMed: 36857592
Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19 [ Life Sci Alliance, 2023, 6(11)e202302106] PubMed: 37699657
Identification of new drugs to counteract anti-spike IgG-induced hyperinflammation in severe COVID-19 [ Life Sci Alliance, 2023, 6(11)e202302106] PubMed: 37699657
Integrative analysis of drug response and clinical outcome in acute myeloid leukemia [ Cancer Cell, 2022, S1535-6108(22)00312-9] PubMed: 35868306
Deregulation and epigenetic modification of BCL2-family genes cause resistance to venetoclax in hematologic malignancies [ Blood, 2022, blood.2021014304] PubMed: 35704690
Interleukin 33-mediated inhibition of A-type K+ channels induces sensory neuronal hyperexcitability and nociceptive behaviors in mice [ Theranostics, 2022, 12(5):2232-2247] PubMed: 35265208
Targeting cellular iron homeostasis with ironomycin in diffuse large B cell lymphoma [ Cancer Res, 2022, canres.0218.2021] PubMed: 35078814
Evaluation of the Synergistic Potential of Simultaneous Pan-or Isoform-Specific BET and SYK Inhibition in B-Cell Lymphoma: An In Vitro Approach. Cancers [ Cancers, 2022, 14(19), 4691] PubMed: None

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。