Entospletinib (GS-9973)

製品コードS7523 バッチS752304

印刷

化学情報

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）

Clear solution

4%DMSO 1 30%PEG300 2 5%Tween80 3 61%ddH2O

2.5mg/ml

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	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.

プロトコル(参考用のみ)

キナーゼアッセイ	Kinase Assays
キナーゼアッセイ	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.
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

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
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。

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。