Target intelligence / Profile preview

DNA (targeted by ifosfamide-derived reactive intermediates) (None)

Target
None
Molecular classification
Other, Nucleic acid
01

Overview

DNA is a double-stranded nucleic acid that serves as the genetic blueprint in cells. DNA is the primary target of alkylating agents such as ifosfamide, which is activated in the liver to produce reactive intermediates like ifosforamide mustard that covalently modify DNA bases, predominantly at the N-7 position of guanine. This alkylation results in cross-linking of DNA strands, causing inhibition of DNA replication and transcription, ultimately leading to tumor cell death. Damage to DNA can be measured by assays such as the COMET assay and is a core mechanism underlying the cytotoxic effects of this class of chemotherapy drugs. Risks include mutagenic effects, neurotoxicity (especially encephalopathy), urotoxicity, and hematological suppression[1][2][3][5][7][8].

Other names
DNA (deoxyribonucleic acid)cellular DNAgenomic DNA
02

Mechanism of action

Formation of cytotoxic DNA cross-links via alkylation at N-7 guanine positions by metabolites (e.g., ifosforamide mustard) Induction of apoptosis and cell death due to impaired DNA replication and transcription

03

Biological functions

Genetic information storageReplicationTranscription template
04

Disease associations

Cancer (targeted for cytotoxic DNA damage in chemotherapy)Other (chemically induced DNA damage is relevant to mutagenesis and other diseases)
05

Safety considerations

Mutagenesis (secondary malignancies)Neurotoxicity (from metabolites such as chloroacetaldehyde)Urotoxicity (from acrolein, a metabolite)Bone marrow suppressionHemorrhagic cystitis
06

Interacting drugs

Ifosfamide

3 more in the full profile.

07

Biomarkers

DNA damage markers (e.g., COMET assay)DNA adduct quantification

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