Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1 (also known as Myt1 kinase))

Protein kinase, membrane-associated tyrosine/threonine 1 (PKMYT1) is a serine/threonine protein kinase belonging to the Wee family. It is a membrane-associated enzyme that negatively regulates the G2/M transition during the cell cycle by phosphorylating cyclin-dependent kinase 1 (CDK1) at threonine 14 and tyrosine 15 residues. This phosphorylation inhibits CDK1 activity and prevents premature entry into mitosis. While dispensable for normal cell cycles under unperturbed conditions, PKMYT1 becomes essential for checkpoint recovery after DNA damage and is critical in certain genetically vulnerable cancers—particularly those with CCNE1 amplification—where its inhibition can lead to synthetic lethality. The first selective inhibitor targeting this enzyme (RP‑6306) has entered clinical trials as a potential precision therapy for solid tumors characterized by specific genetic alterations.

Other names

PKMYT1Myt1 kinaseMembrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase

Inhibition of PKMYT1 leads to loss of CDK1 inhibition, resulting in unscheduled mitosis and cell death—especially synthetic lethality in tumors with CCNE1 amplification or certain mutations such as KRAS/p53, FBXW7, PPP2R1A.