| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg |
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Purity: ≥98%
Tirabrutinib (formerly ONO-4059; GS4059; ONO-WG-307; Steboronine) is a novel, potent, highly selective, covalent/irreversible and orally bioavailable BTK (Bruton agammaglobulinemia tyrosine kinase) inhibitor with anticancer activity. It has been approved in Japan since March 2020 for the treatment of recurrent or refractory primary central nervous system lymphoma. It inhibits BTK with an IC50 of 2.2 nM. Tirabrutinib inhibits B-cell development by covalently attaching to BTK within B cells, which stops B-cell receptor signaling. This means that this substance might prevent B-cell cancers from spreading. As a cytoplasmic tyrosine kinase belonging to the Tec family, BTK is crucial for B lymphocyte activation, development, proliferation, and survival.
| Targets |
BMX (IC50 = 6 nM); BTK (IC50 = 6.8 nM); TEC (IC50 = 48 nM); TXK (IC50 = 92 nM); BLK (IC50 = 0.3 μM); ERBB4 (IC50 = 0.77 μM); EGFR (IC50 = 3.02 μM); JAK3 (IC50 = 5.52 μM); ERBB2 (IC50 = 7.31 μM)
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| ln Vitro |
Tirabrutinib (0.1-1000 nM or 0.001-100 nM; 72 h) has IC50 values of 9.127 nM and 17.10 nM, respectively, which limit the growth of OCI-L Y10 and SU-DHL-6 cells[1].
Tirabrutinib (0.5, 5, 50 μM; 24, 48 h) induces apoptosis in SU-DHL-6 cells; however, it requires a high dosage and long administration (48 hours of incubation at a concentration of up to 50 μM)[1]. Tirabrutinib (300 nM, 72 h) causes caspase-3 and PARP cleavage in TMD8 cells[2]. |
| ln Vivo |
Tirabrutinib (10 mg/kg; p.o.; single) enters the brain and plasma quickly, reaching its Cmax two hours after administration (blood Cmax = 339.53 ng/mL, brain Cmax = 28.9 ng/mL)[1].
Tirabrutinib (6, 20 mg/kg; p.o.; single daily for 3 weeks) inhibits the growth of tumors in vivo[2]. |
| Cell Assay |
Cell Line: SU-DHL-6 and OCI-L Y10 cells
Concentration: 0.1-1000 nM; 0.001 nM-100 nM Incubation Time: 72 h Result: Showed good anti-proliferative activity with IC50s of 9.127 nM, and 17.10 nM for OCI-L Y10 and SU-DHL-6 cells, respectively. |
| Animal Protocol |
Male SD rats (219.0–260.5g)
10 mg/kg Oral administration; single. |
| References |
| Molecular Formula |
C25H22N6O3
|
|---|---|
| Molecular Weight |
454.490
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| Exact Mass |
454.18
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| Elemental Analysis |
C, 66.07; H, 4.88; N, 18.49; O, 10.56
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| CAS # |
1351636-18-4
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| Related CAS # |
Tirabrutinib hydrochloride;1439901-97-9;ONO-4059 analog;1351635-67-0
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| Appearance |
White to off white powder
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| SMILES |
CC#CC(=O)N1CC[C@H](C1)N2C3=NC=NC(=C3N(C2=O)C4=CC=C(C=C4)OC5=CC=CC=C5)N
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| InChi Key |
SEJLPXCPMNSRAM-GOSISDBHSA-N
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| InChi Code |
InChI=1S/C25H22N6O3/c1-2-6-21(32)29-14-13-18(15-29)31-24-22(23(26)27-16-28-24)30(25(31)33)17-9-11-20(12-10-17)34-19-7-4-3-5-8-19/h3-5,7-12,16,18H,13-15H2,1H3,(H2,26,27,28)/t18-/m1/s1
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| Chemical Name |
6-amino-9-[(3R)-1-but-2-ynoylpyrrolidin-3-yl]-7-(4-phenoxyphenyl)purin-8-one
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| Synonyms |
ONO-4059; GS4059; ONO-WG-307; ONO4059; GS-4059;ONO 4059; ONO-4059; GS 4059; ONO WG-307
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: ≥ 100 mg/mL (~220.0 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.50 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.50 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.50 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2003 mL | 11.0013 mL | 22.0027 mL | |
| 5 mM | 0.4401 mL | 2.2003 mL | 4.4005 mL | |
| 10 mM | 0.2200 mL | 1.1001 mL | 2.2003 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT02457598 | Active Recruiting |
Drug: Tirabrutinib Drug: Idelalisib |
B-cell Malignancies | Gilead Sciences | June 16, 2015 | Phase 1 |
| NCT04947319 | Recruiting | Drug: Tirabrutinib | Refractory Primary Central Nervous System Lymphoma Primary CNS Lymphoma |
Ono Pharmaceutical Co. Ltd | December 29, 2021 | Phase 2 |
| NCT02983617 | Completed | Drug: Tirabrutinib Drug: Entospletinib |
Chronic Lymphocytic Leukemia | Gilead Sciences | April 6, 2017 | Phase 2 |
| NCT02968563 | Completed | Drug: Tirabrutinib Drug: Idelalisib |
Chronic Lymphocytic Leukemia | Gilead Sciences | December 13, 2016 | Phase 2 |
| NCT02626026 | Completed | Drug: Tirabrutinib Drug: Placebo |
Rheumatoid Arthritis | Gilead Sciences | January 26, 2016 | Phase 1 |
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