Membrane-associated tyrosine-threonine-protein kinase (PKMYT1) (PKMYT1)

Membrane-associated tyrosine-threonine-protein kinase (PKMYT1) is a critical regulator of the cell cycle, specifically governing the G2/M transition. It functions by phosphorylating and thereby inhibiting the Cyclin-dependent kinase 1 (CDK1) complex, preventing cells from entering mitosis prematurely (UniProt P23919). In many cancers, particularly those with CCNE1 (Cyclin E1) amplification, cells become highly dependent on PKMYT1 to manage replication stress and prevent mitotic catastrophe (Gallo et al., Nature 2022). Therapeutic strategies focus on small molecule inhibitors of the PKMYT1 protein to induce synthetic lethality in these specific genetic backgrounds. By inhibiting PKMYT1, these drugs force cancer cells into a premature and lethal mitosis, making it a promising target for precision oncology. Clinical candidates like lunresertib (RP-6306) are currently being evaluated in trials for patients with CCNE1-amplified tumors (NCT04855656).

Other names

Myt1 kinaseProtein kinase membrane-associated tyrosine-threonine 1PKMYT1MYT1PKMYT1 mRNA

Inhibition of PKMYT1 kinase activity prevents the inhibitory phosphorylation of CDK1, leading to premature entry into mitosis and subsequent cell death, particularly in cells with CCNE1 amplification.