Target intelligence / Profile preview

Protein kinase, membrane-associated tyrosine- and threonine-specific 1 (PKMYT1)

Target
PKMYT1
Molecular classification
Enzyme, Serine/threonine kinase, Tyrosine kinase, Wee1 family kinase
01

Overview

Protein kinase, membrane-associated tyrosine- and threonine-specific 1 (PKMYT1) is a membrane-associated kinase of the Wee1 family that negatively regulates cell cycle progression by phosphorylating and inactivating cyclin-dependent kinase 1 (CDK1) at threonine 14 and tyrosine 15. Predominantly localized to the endoplasmic reticulum and Golgi apparatus, PKMYT1 functions in the cytoplasm and is essential for maintaining the G2/M checkpoint, preventing premature mitosis when DNA damage or errors are detected. It is frequently overexpressed in several cancer types, where it supports tumor cell proliferation, migration, and drug resistance, making it a promising therapeutic target for inhibitors in oncology research. PKMYT1 is regulated by polo-like kinase 1 (Plk1) and participates in a feedback loop with Wee1 and Cdc25 phosphatases to tightly control CDK1 activation and cell cycle transitions.

Other names
Myt1 kinasePKMYT1Membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinaseprotein kinase Myt1membrane-associated tyrosine/threonine 1 kinase
02

Mechanism of action

Inhibition of CDK1 activity via phosphorylation at Thr14 and Tyr15, preventing premature mitosis. Checkpoint abrogation: Some drugs promote unscheduled CDK1 activation leading to cell death in cancer cells.

03

Biological functions

Cell cycle regulationG2/M checkpoint controlCDK1 inhibitionPhosphorylation of CDK1 at Thr14 and Tyr15Maintenance of genomic stabilityRegulation of mitosis and entry into meiosis
04

Disease associations

Cancer (colorectal, prostate, hepatocellular, renal, lung, triple-negative breast cancers)Drug resistance in tumorsCell proliferation regulationPotential role in neurodevelopment, but mainly oncology-related
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Safety considerations

On-target cytotoxicity: Unscheduled CDK1 activation may cause cell death in normal tissues if not selectively targetedTumor cell resistance: PKMYT1 may mediate resistance to Wee1 inhibitorsPotential loss of checkpoint control and genomic stability with inhibition
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Interacting drugs

PD0166285

2 more in the full profile.

07

Biomarkers

PKMYT1 gene/protein overexpression in specific cancer subtypes (e.g., CCNE1-amplified tumors, triple-negative breast cancer, colorectal cancer)Phosphorylation status of CDK1 (Thr14, Tyr15) as indirect marker of PKMYT1 pathway activity

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