| 产品描述： | Tirabrutinib (ONO-4059) is an orally active Bruton’s Tyrosine Kinase (BTK) inhibitor (can cross the blood-brain barrier (BBB)), with an IC50 of 6.8 nM. Tirabrutinib irreversibly and covalently binds to BTK and inhibits aberrant B cell receptor signaling. Tirabrutinib can be used in studies of autoimmune diseases and hematological malignancies |
| 靶点： |
BTK |
| 体外研究： |
Tirabrutinib (0.1-1000 nM or 0.001-100 nM; 72 h) inhibits the proliferation of OCI-L Y10 and SU-DHL-6 cells with IC50s of 9.127 nM, and 17.10 nM, respectively. Tirabrutinib (0.5, 5, 50 μM; 24, 48 h) induces SU-DHL-6 cells apoptosis needs high dosage and prolonged administration (concentration up to 50 μM and incubates for 48 h). Tirabrutinib (300 nM, 72 h) induces caspase-3 and PARP cleavage in TMD8 cells. Cell Proliferation 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. Apoptosis Analysis Cell Line: SU-DHL-6 cells Concentration: 0.5, 5, 50 μM Incubation Time: 24, 48 h Result: Induced cell apoptosis when concentration up to 50 μM and incubated for 48 h. Western Blot Analysis Cell Line: TMD8 cells Concentration: 300 nM Incubation Time: 72 h Result: Induced caspase-3 and PARP cleavage. |
| 体内研究： |
Tirabrutinib (10 mg/kg; p.o.; single) is rapidly absorbed into plasma and brain, and reaches Cmax (blood Cmax =339.53 ng/mL; brain Cmax =28.9 ng/mL) 2 hours post administration. Tirabrutinib (6, 20 mg/kg; p.o.; single daily for 3 weeks) shows inhibition of tumour growth in vivo. Animal Model: Male SD rats (219.0–260.5g). Dosage: 10 mg/kg Administration: Oral administration; single. Result: Pharmacokinetic Parameters of Tirabrutinib in male SD rats Animal Model: Immunodeficiency (SCID) mice (mouse xenograft model). Dosage: 6, 20 mg/kg Administration: Oral administration; single daily for 3 weeks. Result: Inhibited tumour growth, and when dosage up to 20 mg/kg, a complete tumor suppression at day 14. |
| 参考文献： |
1. Yu H, et al. Bruton's tyrosine kinase inhibitors in primary central nervous system lymphoma-evaluation of anti-tumor efficacy and brain distribution. Transl Cancer Res. 2021 May;10(5):1975-1983. 2. Kozaki R, et al. Responses to the Selective Bruton's Tyrosine Kinase (BTK) Inhibitor Tirabrutinib (ONO/GS-4059) in Diffuse Large B-cell Lymphoma Cell Lines. Cancers (Basel). 2018 Apr 23;10(4):127. 3. Liclican A, et al. Biochemical characterization of tirabrutinib and other irreversible inhibitors of Bruton's tyrosine kinase reveals differences in on - and off - target inhibition. Biochim Biophys Acta Gen Subj. 2020 Apr;1864(4):129531. 4. Dhillon S. Tirabrutinib: First Approval. Drugs. 2020 Jun;80(8):835-840. |
| 溶解性： |
soluble in DMSO |
| 保存条件： |
-20℃ |
| 配置溶液浓度参考： |
|
1mg |
5mg |
10mg |
| 1 mM |
2.2 ml |
11.002 ml |
22.003 ml |
| 5 mM |
0.44 ml |
2.2 ml |
4.401 ml |
| 10 mM |
0.22 ml |
1.1 ml |
2.2 ml |
| 50 mM |
0.044 ml |
0.22 ml |
0.44 ml |
|
| 注意： |
部分产品我司仅能提供部分信息，我司不保证所提供信息的权威性，仅供客户参考交流研究之用。 |
上海工商
危险品化学品经营许可证（不带存储）
营业执照(三证合一)
北京