PDZ-binding kinase (PBK) (PBK)

PDZ-binding kinase (PBK), also known as T-LAK cell-originated protein kinase (TOPK), is a serine/threonine protein kinase belonging to the MAPKK-like family that is primarily active during mitosis [1, 3]. It plays a critical role in cell cycle progression, DNA damage repair, and the regulation of apoptosis, particularly in rapidly dividing cells [7, 14]. While its expression in normal adult tissues is largely restricted to the testis and placenta, PBK is significantly upregulated in a wide range of human malignancies, including glioblastoma, hepatocellular carcinoma, and breast cancer [4, 5, 17]. This overexpression is frequently associated with aggressive tumor phenotypes, poor clinical prognosis, and resistance to conventional therapies like radiation and chemotherapy [1, 19]. Due to its restricted normal expression and high tumor prevalence, PBK is considered a promising therapeutic target and a potential cancer/testis antigen [8, 16]. Several small-molecule inhibitors, such as OTS964 and HI-TOPK-032, have demonstrated potent anti-tumor activity in preclinical models by inducing mitotic catastrophe and programmed cell death [3, 19].

Other names

TOPKT-LAK cell-originated protein kinaseSPKCT84HEL164Nori-3MAPKK-like protein kinaseCancer/testis antigen 84Spermatogenesis-related protein kinase

Inhibition of the catalytic kinase activity of PBK/TOPK, leading to cell cycle arrest at the G2/M phase and induction of apoptosis in highly proliferative cells.