Tirabrutinib (ONO-4059) 是一种口服有效的高选择性 Bruton’s TyROSine Kinase (BTK) 抑制剂 (能透过血脑屏障),其 IC50 值为 6.8 nM。Tirabrutinib 不可逆共价结合 BTK 并抑制异常 B 细胞受体信号传导。Tirabrutinib 可用于自身免疫性疾病和血液学恶性肿瘤的研究。
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.
体外活性
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[1]. 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)[1]. Tirabrutinib (300 nM, 72 h) induces caspase-3 and PARP cleavage in TMD8 cells[2].
体内活性
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[1]. Tirabrutinib (6, 20 mg/kg; p.o.; single daily for 3 weeks) shows inhibition of tumour growth in vivo[2].
Cas No.
1351636-18-4
分子式
C25H22N6O3
分子量
454.48
别名
ONO-4059;GS-4059;Velexbru
储存和溶解度
DMSO:90mg/mL (198mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years