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• 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

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本计算器可帮助您计算出特定溶液中溶质的质量、溶液浓度和体积之间的关系，公式为：

质量 (mg) = 浓度 (mM) x 体积 (mL) x 分子摩尔量 (g/mol)

• pg ng μg mg g kg =
  fM pM nM μM mM M *
  nL μL mL L *