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Target intelligence / Profile preview
Ataxia Telangiectasia and Rad3-Related Protein Kinase (ATR)
- Target
- ATR
- Molecular classification
- Enzyme, Protein Kinase, Serine/threonine-specific protein kinase, Phosphatidylinositol 3-kinase-related kinase (PIKK) family
01
Overview
Ataxia Telangiectasia and Rad3-Related Protein Kinase (ATR) is a serine/threonine-specific protein kinase and a master regulator of the cellular response to DNA damage and replication stress. It belongs to the PIKK family and is activated by single-stranded DNA (ssDNA) coated with Replication Protein A (RPA) at stalled replication forks. Upon activation, ATR phosphorylates multiple downstream targets involved in cell cycle arrest, DNA repair, and apoptosis, ensuring genome integrity. Due to its essential role in cancer cell survival under replication stress, ATR is an attractive therapeutic target, and ATR inhibitors are being developed as potential cancer treatments, especially for tumors with deficiencies in other DNA repair pathways.
- Other names
- Ataxia telangiectasia and Rad3-related proteinFRAP-related protein 1 (FRP1)Serine/threonine-protein kinase ATR
02
Mechanism of action
ATR inhibitors block the ATR pathway, preventing cell cycle arrest and DNA repair in response to DNA damage. This leads to increased sensitivity of cancer cells to DNA-damaging agents or replication stress.
03
Biological functions
DNA damage responseCell cycle checkpoint controlDNA repairReplication fork stabilizationApoptosis regulationGenome integrityResponse to mechanical stress
04
Disease associations
CancerGenetic disorders related to DNA repair deficienciesChromosomal instability syndromes
05
Safety considerations
MyelosuppressionOff-target effects on other kinasesPotential for drug resistanceBone marrow suppression
06
Biomarkers
ERCC1 expressionBRCA1/2 mutationsPresence of replication stress markersATM deficiency
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