受注:045-509-1970 |
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Synonyms | N/A | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C23H21N7O |
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分子量 | 411.46 | CAS No. | 1229208-44-9 | |
Solubility (25°C)* | 体外 | DMSO | 27 mg/mL warmed with 50ºC water bath (65.61 mM) | |
Water | Insoluble | |||
Ethanol | Insoluble | |||
* <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. |
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. |
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in vitro | GS-9973 shows good bidirectional permeability across Caco-2 cell monolayers in vitro. In cells, GS-9973 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 idelalisib and GS-9973 synergistically inhibits CLL cell viability and further disrupts chemokine signaling. [2] |
in vivo | GS-9973 (1 mg/kg p.o.) shows moderate to high bioavailability in rat and dog. In a rat collagen-induced arthritis model, GS-9973 (1-10 mg/kg p.o.) significantly inhibits ankle inflammation. Moreover, GS-9973 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. |
キナーゼアッセイ | Kinase Assays | |
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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, 0.25% glycerol, 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 test compounds 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 compound inhibition of MV-4-11 cell proliferation. 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. |
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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. |
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]
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 |
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 |
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 |
Establishment and characterization of NCC-UPS4-C1: a novel cell line of undifferentiated pleomorphic sarcoma from a patient with Li-Fraumeni syndrome [ Hum Cell, 2022, 10.1007/s13577-022-00671-y] | PubMed: 35118583 |
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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