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Target intelligence / Profile preview
O6-methylguanine-DNA methyltransferase (MGMT)
- Target
- MGMT
- Molecular classification
- Enzyme, DNA repair enzyme, Transferase
01
Overview
MGMT is a DNA repair enzyme that removes mutagenic alkyl adducts from the O6 position of guanine in DNA. This repair mechanism prevents mutations and drug resistance, particularly to alkylating chemotherapeutic agents like temozolomide. The enzyme's activity is often silenced by promoter methylation in certain cancers, making these tumors more sensitive to alkylating agents. Inhibition of MGMT is a therapeutic strategy to enhance the efficacy of alkylating chemotherapy.
- Other names
- Methylated-DNA-protein-cysteine methyltransferaseO6-alkylguanine DNA alkyltransferase (AGT)
02
Mechanism of action
Direct transfer of alkyl group from O6-methylguanine to a cysteine residue within MGMT, leading to MGMT inactivation.
03
Biological functions
DNA repairGenome stability maintenancePrevention of DNA mismatch during replication and transcription
04
Disease associations
CancerDrug resistance
05
Safety considerations
Increased risk of hydrocephalus or infection after brain tumor surgery when MGMT inhibitors are used in combination with chemotherapy
06
Interacting drugs
Temozolomide
2 more in the full profile.
07
Biomarkers
MGMT promoter methylation statusMGMT protein expression levels
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