生物活性

• 靶点	BTK IC50:2.2nM

• 描述BTK (Bruton Tyrosine Kinase) is a cytoplasmic, non-receptor tyrosine kinase that transmits signals from a variety of cell-surface molecules, including the B-cell receptor (BCR) and tissue homing receptors. BTK is indispensable for B lymphocyte development, differentiation and signaling, and plays a crucial role in B-cell development^[3]. ONO-4059 is a BTK inhibitor. The IC50 of ONO-4059 against BTK kinase was 2.2 nM^[3]. ONO-4059 inhibited the TMD-8 cell growth with the IC50 of 3.59 nM for 72h as determined by a cell viability assay. ONO-4059 also concentration-dependently inhibited BTK phosphorylation with the IC50 of 23.9 nM for 4h^[4]. In a TMD-8 xenograft model established in SCID mice, ONO-4059 was administered orally or mixed in food at doses up to 20 mg/kg/day and animals were dosed QD or BD. For the groups that treatment started when tumor volume was 100 - 200mm³, tumor growth inhibition of ONO-4059 treated groups was 23% in QD, 72.9% in BD and 100% in dose mixed in food, respectively. For the groups that treatment started when tumor volume was 400 - 450mm³, no growth inhibition was observed in the QD group and growth inhibitions of 27.5% in BD and 100% in dose mixed in food were observed^[5]. In another study of TMD-8 xenograft model, ONO-4059 was administered via mixed diet at an indicated relative content of 0.0037%. This dose resulted in tumor growth inhibition of 56.1% as a single agent and significantly enhanced the anti-tumor activity of Rituximab^[6].

• 动物研究
  剂量	Mice: 3 mg/kg - 30 mg/kg[3] (p.o.)
  给药途径	p.o.