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Synonyms | GS-4059 | Storage (From the date of receipt) |
3 years -20°C powder 1 years -80°C in solvent |
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化学式 | C25H22N6O3.HCl |
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分子量 | 490.94 | CAS No. | 1439901-97-9 | |
Solubility (25°C)* | 体外 | DMSO | 98 mg/mL (199.61 mM) | |
Ethanol | 1 mg/mL (2.03 mM) | |||
Water | 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 | Tirabrutinib Hydrochloride (ONO-4059, GS-4059) is a highly potent and selective BTK inhibitor with an IC50 of 2.2 nM. |
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in vitro | ONO-4059 covalently binds to BTK, and reversibly blocks BCR signaling and B-cell proliferation and activation[1]. It has greater selectivity for BTK than Lck, Fyn, LynA and ONO/GS-4059 only inhibits anti-IgM-induced B-cell activation in a concentration-dependent manner but not inhibit anti-CD3/CD28-induced activation of T-lymphocytes from human PBMCs. ONO/GS-4059 inhibits cell proliferation in some malignant B-cell lines but also induces classical apoptosis at nanomolar concentration in the activated-B cell (ABC) DLBCL cell line, TMD8[4]. |
in vivo | ONO-4059 demonstrates therapeutic efficacy in a mouse CIA model by suppressing generation of inflammatory chemokines and cytokines including IL-6, IL-8, and TNFα by monocytes, and accompanied by regression of cartilage erosion, bone damage, and pannus formation[1]. In pre-clinical models, and in the clinic in both CLL and NHL patients, It exerts its anti-tumour activity, with a favourable safety profile along with promising efficacy over a long duration[3]. |
細胞アッセイ | 細胞株 | DLBCL cell lines TMD8 cells |
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濃度 | 320 nM | |
反応時間 | 48 h | |
実験の流れ | Cells are treated with idelalisib (420 nM), ONO/GS-4059 (320 nM) or in combination for 48 hours and apoptosis is assessed by FITC Annexin V staining, and measured by flow cytometry | |
動物実験 | 動物モデル | Male CB17-SCID mice |
投薬量 | 5 and 10 mg/kg | |
投与方法 | by oral gavage |
Structure of BTK kinase domain with the second-generation inhibitors acalabrutinib and tirabrutinib [ PLoS One, 2023, 18(8):e0290872] | PubMed: 37651403 |
Bruton's TK regulates myeloid cell recruitment during acute inflammation [ Br J Pharmacol, 2022, 179(11):2754-2770] | PubMed: 34897650 |
Assessment of the effects of Syk and BTK inhibitors on GPVI-mediated platelet signaling and function [ Am J Physiol Cell Physiol, 2021, 320(5):C902-C915] | PubMed: 33689480 |
Bruton's Tyrosine Kinase Inhibition Effectively Protects Against Human IgE-mediated Anaphylaxis [ J Clin Invest, 2020, 2;138448] | PubMed: 32484802 |
Effects of Inhibitors against Syk-BTK-PI3K Signaling on Platelet Function [ ScholarsArchive@OSU, 2020, 51] | PubMed: N/A |
Effects of Inhibitors against Syk-BTK-PI3K Signaling on Platelet Function [ ScholarsArchive@OSU, 2020, None] | PubMed: None |
Effect of Bruton's tyrosine kinase inhibitors on platelet aggregation in patients with acute myocardial infarction. [ Thromb Res, 2019, 179:64-68] | PubMed: 31082751 |
Optimizing Platelet GPVI Inhibition versus Haemostatic Impairment by the Btk Inhibitors Ibrutinib, Acalabrutinib, ONO/GS-4059, BGB-3111 and Evobrutinib [Denzinger V, et al. Thromb Haemost, 2019, 10.1055/s-0039-1677744] | PubMed: 30685871 |
Sensitive Detection of the Natural Killer Cell-Mediated Cytotoxicity of Anti-CD20 Antibodies and Its Impairment by B-Cell Receptor Pathway Inhibitors [Hassenrück F, et al. Biomed Res Int, 2018, 2018:1023490] | PubMed: 29750146 |
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。