WEE1 G2 checkpoint kinase and WEE2 oocyte meiosis inhibiting kinase (WEE1/2)

WEE1 and WEE2 (also known as WEE1B) are critical dual-specificity kinases that regulate the cell cycle by phosphorylating and inactivating cyclin-dependent kinases (CDKs). WEE1 is the primary gatekeeper of the G2/M checkpoint in somatic cells, where it phosphorylates CDK1 at the Tyr15 residue to prevent premature entry into mitosis, especially in the presence of DNA damage (1.2.1, 1.5.2). WEE2 is primarily expressed in germ cells and plays a specialized role in maintaining meiotic arrest in oocytes (1.3.1, 1.3.5). In oncology, WEE1 is a high-priority therapeutic target because many cancer cells lack a functional G1 checkpoint, often due to TP53 mutations, and become heavily dependent on the G2/M checkpoint for DNA repair (1.1.1, 1.2.4). Inhibiting WEE1 forces these cells into mitotic catastrophe, where they enter mitosis with unrepaired DNA damage, leading to selective cell death (1.2.2, 1.5.3). Clinical development of WEE1 inhibitors like adavosertib and azenosertib has shown promise in treating various solid tumors, particularly when combined with DNA-damaging agents (1.4.1, 1.4.2). Additionally, WEE2 is being explored as a target for non-hormonal contraception due to its essential role in oocyte maturation and fertilization (1.3.5).

Other names

WEE1WEE2WEE1AWEE1BWEE1huOocyte meiosis inhibiting kinaseOOMD5OZEMA5

Inhibition of WEE1/2 kinase activity prevents the inhibitory phosphorylation of CDK1 at the Tyr15 residue, leading to premature entry into mitosis and subsequent mitotic catastrophe in cells with DNA damage.