Acalabrutinib 是一种不可逆的、高效的、具有口服活性、选择性的第二代BTK抑制剂。它与 BTK 的 ATP 结合口袋中的 Cys481 共价结合。它在慢性淋巴细胞性白血病 (CLL) 小鼠模型中显示出强大的靶向作用和功效。

Acalabrutinib, also known as ACP-196, is an orally available inhibitor of Bruton's tyrosine kinase (BTK) with potential antineoplastic activity. Upon administration, ACP-196 inhibits the activity of BTK and prevents the activation of the B-cell antigen receptor (BCR) signaling pathway. This prevents both B-cell activation and BTK-mediated activation of downstream survival pathways. This leads to an inhibition of the growth of malignant B cells that overexpress BTK. BTK, a member of the src-related BTK/Tec family of cytoplasmic tyrosine kinases, is overexpressed in B-cell malignancies; it plays an important role in B lymphocyte development, activation, signaling, proliferation and survival.

小鼠口服ACP-196,剂量依赖性抑制CD19+脾细胞中anti-IgM诱导的CD86表达,ED50为0.34 mg/kg.在处理后3 h,ACP-196抑制了>90%的CD86表达水平.

Acalabrutinib不抑制EGFR、ITK和TEC,对EGFR在Y1068和Y1173位点的磷酸化没有影响。Acalabrutinib比ibrutinib具有更高的IC50值,并几乎对 ITK,EGFR,ERBB2,ERBB4,JAK3,BLK,FGR,FYN,HCK,LCK,LYN,SRC以及YES1的激酶活性没有抑制作用在初级人源慢性淋巴细胞白血病细胞的体外信号检测中,Acalabrutinib抑制下游靶标ERK、IKB、AKT的酪氨酸磷酸化。

1420477-60-6

C26H23N7O2

465.517

阿可替尼;ACP-196

Ethanol:53 mg/mL(113.9 mM)
DMSO:86 mg/mL (184.7 mM)
Powder: -20°C for 3 years
In solvent: -80°C for 2 years