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This entry refers to a broad and heterogeneous collection of biological entities rather than a single, defined therapeutic target. It encompasses various enzymes in the oxidoreductase class, which catalyze electron transfer reactions, as well as nucleophilic biomolecules such as DNA and proteins containing reactive cysteine or lysine residues (BRENDA Enzyme Database, https://www.brenda-enzymes.org; PubChem, https://pubchem.ncbi.nlm.nih.gov). These entities are often the collective targets of electrophilic drugs, alkylating agents, and reactive oxygen species that form covalent bonds or alter the redox state of the cell (DrugBank Online, https://go.drugbank.com/drugs/DB00305). Because this category lacks specificity, it is frequently associated with drugs that exhibit pleiotropic effects and significant off-target toxicity (National Cancer Institute, https://www.cancer.gov). In a pharmacological context, this designation is typically used to describe the multi-target or non-specific interactions of cytotoxic agents used in chemotherapy. The interaction with nucleophilic biomolecules often leads to DNA cross-linking or protein dysfunction, which are primary mechanisms for inducing cell death in rapidly dividing cancer cells. Oxidoreductases within this group may include enzymes like NADPH-cytochrome P450 reductase, which are involved in the bioactivation of certain prodrugs. Overall, this classification serves as a placeholder for complex chemical interactions that do not map to a single protein receptor or enzyme.
Covalent modification of nucleophilic sites and modulation of redox-active enzymes
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