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ONO-4059 hydrochloride

Cat. No. M5257
ONO-4059 hydrochloride Structure
Synonym:

GS-4059

Size Price Availability Quantity
5mg USD 107 In stock
10mg USD 197 In stock
50mg USD 640 In stock
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Quality Control
  • Current batch:
  • Purity >99%
  • COA
  • MSDS
Biological Activity

In vitro: ONO-4059 covalently binds to BTK, and reversibly blocks BCR signaling and B-cell proliferation and activation. 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.

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. 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.

Protocol
Cell Experiment
Cell lines DLBCL cell lines TMD8 cells
Preparation 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.
Concentrations 320 nM
Incubation time 48 h
Animal Experiment
Animal models Male CB17-SCID mice
Formulation 5% (v/v) N-Methyl-2-pyrrolidone (NMP) / 55% (v/v) Polyethylene Glycol 300 (PEG) 300 / 40% (v/v) Water / 1% (w/v) Vitamin E D-α-Tocopherol Polyethylene Glycol 1000 Succinate (TPGS)
Dosages 5 and 10 mg/kg
Administration oral gavage
Conversion of different model animals based on BSA (Value based on data from FDA Draft Guidelines)
Species Mouse Rat Rabbit Guinea pig Hamster Dog
Weight (kg) 0.02 0.15 1.8 0.4 0.08 10
Body Surface Area (m2) 0.007 0.025 0.15 0.05 0.02 0.5
Km factor 3 6 12 8 5 20
Animal A (mg/kg) = Animal B (mg/kg) multiplied by  Animal B Km
Animal A Km

For example, to modify the dose of resveratrol used for a mouse (22.4 mg/kg) to a dose based on the BSA for a rat, multiply 22.4 mg/kg by the Km factor for a mouse and then divide by the Km factor for a rat. This calculation results in a rat equivalent dose for resveratrol of 11.2 mg/kg.

Chemical Information
Molecular Weight 490.94
Formula C25H22N6O3.HCl
CAS Number 1439901-97-9
Purity >99%
Solubility 98 mg/mL in DMSO
Storage at -20°C
References

PI3Kδ inhibitor idelalisib in combination with BTK inhibitor ONO/GS-4059 in diffuse large B cell lymphoma with acquired resistance to PI3Kδ and BTK inhibitors.
Yahiaoui A, et al. PLoS One. 2017 Feb 8;12(2):e0171221. PMID: 28178345.

Bruton tyrosine kinase inhibitor ONO/GS-4059: from bench to bedside.
Wu J, et al. Oncotarget. 2017 Jan 24;8(4):7201-7207. PMID: 27776353.

Anti-tumor efficacy study of the Bruton's tyrosine kinase (BTK) inhibitor, ONO/GS-4059, in combination with the glycoengineered type II anti-CD20 monoclonal antibody obinutuzumab (GA101) demonstrates superior in vivo efficacy compared to ONO/GS-4059 in combination with rituximab.
Yasuhiro T, et al. Leuk Lymphoma. 2017 Mar;58(3):699-707. PMID: 27684575.

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ONO-4059 analogue

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  Catalog
Abmole Inhibitor Catalog 2017




Keywords: ONO-4059 hydrochloride, GS-4059 supplier, BTK, inhibitors

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