tirabrutinib(ONO-4059) hydrochloride

Catalog No.S8166 Batch:S816601

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Technical Data

Formula

C25H22N6O3.HCl
Molecular Weight 490.94 CAS No. 1439901-97-9
Solubility (25°C)* In vitro 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.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description Tirabrutinib Hydrochloride (ONO-4059, GS-4059) is a highly potent and selective BTK inhibitor with an IC50 of 2.2 nM.
Targets
BTK [1]
2.2 nM
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].

Protocol (from reference)

Cell Assay:[2]
  • Cell lines

    DLBCL cell lines TMD8 cells

  • Concentrations

    320 nM

  • Incubation Time

    48 h

  • Method

    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
Animal Study:[2]
  • Animal Models

    Male CB17-SCID mice

  • Dosages

    5 and 10 mg/kg

  • Administration

    by oral gavage

Selleck's tirabrutinib(ONO-4059) hydrochloride has been cited by 9 publications

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

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

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