Target intelligence / Profile preview

DNA cross-link (specifically, phosphoramide mustard-induced DNA cross-link)

Molecular classification
Other (DNA adduct/covalent DNA modification)
01

Overview

DNA cross-linking via alkylation by cyclophosphamide refers to the formation of covalent bonds between two strands of DNA, predominantly at guanine N-7 positions, caused by the active cyclophosphamide metabolite phosphoramide mustard. This leads to inter- and intrastrand cross-links, blocking DNA replication and transcription, and ultimately resulting in cell cycle arrest and apoptosis. This molecular lesion is the primary mediator of cyclophosphamide's cytotoxic effects against cancer and certain immune cells. DNA cross-linking is not a protein or receptor, but a chemical modification of DNA, and represents a cytotoxic damage mechanism rather than a discrete druggable "target"[1][2][3][4][5][6][7][8].

Other names
DNA–DNA cross-linkinterstrand DNA cross-linkDNA alkylation by cyclophosphamideguanine N-7 cross-link
02

Mechanism of action

Formation of covalent bonds (alkylation) with DNA at the N-7 position of guanine, leading to DNA cross-links that block replication and transcription, resulting in apoptosis[1][2][3][4][5][6].

03

Biological functions

Cell deathApoptosisCell cycle arrestInhibition of DNA replication and transcription
04

Disease associations

Cancer
05

Safety considerations

Cytotoxicity to normal rapidly dividing cells (bone marrow suppression, mucositis)Risk of secondary malignancies (due to mutagenic DNA damage)Hemorrhagic cystitis (due to acrolein, a metabolite)InfertilityImmunosuppression[2][4][5][6]
06

Interacting drugs

Cyclophosphamide

1 more in the full profile.

07

Biomarkers

DNA cross-link adduct measurement (e.g., N-7-guanine adducts, G-NOR-G)[3]Functional DNA repair status (e.g., Fanconi anemia pathway status in some settings)[3]

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