Cellular nucleophilic proteins

Cellular nucleophilic proteins do not represent a single therapeutic target but rather a broad class of proteins containing nucleophilic functional groups, such as sulfhydryl (cysteine), amino (lysine), or imidazole (histidine) groups. These proteins are frequently the unintended or non-specific targets of electrophilic drugs, particularly alkylating agents used in chemotherapy. When these drugs react with nucleophilic sites on proteins, they can cause structural damage, enzymatic inhibition, or trigger cellular stress responses. Because this term encompasses a vast array of proteins across various cellular pathways, it is generally considered too non-specific to be classified as a distinct therapeutic target in modern drug discovery. Instead, it is often used in the context of toxicology and the mechanism of action for non-selective cytotoxic agents that form covalent bonds with various cellular constituents, including DNA and proteins (Source: Goodman & Gilman's The Pharmacological Basis of Therapeutics; PubChem).

Other names

Nucleophilic cellular proteinsNucleophilic protein targets

Covalent modification via alkylation or adduction of nucleophilic amino acid side chains (e.g., cysteine, lysine, histidine).