AKR7 Inhibitors

Chemical inhibitors of AKR7 can interfere with the protein's function through various mechanisms. Acrolein, for example, can form adducts with cysteine residues in the active site of AKR7, perturbing the catalytic mechanism that is central to the protein's detoxification function. Similarly, cinnamaldehyde can bind to nucleophilic amino acid residues, leading to inhibition through steric hindrance and modification of the active site conformation. Ethacrynic acid, known for its ability to inhibit glutathione S-transferases, can also inhibit AKR7 by covalently modifying key cysteine residues, obstructing the catalytic reduction of substrates. Phloretin acts as a competitive inhibitor by binding to the substrate binding sites of AKR7, thereby blocking substrate access and inhibiting the enzyme's function. Sulforaphane targets AKR7 by altering thiol groups within the active site, modifying the enzyme's structure and inhibiting its activity.

Continuing with the variety of mechanisms by which chemicals can inhibit AKR7, hesperidin can bind to allosteric sites on the protein, inducing conformational changes that reduce substrate affinity, which leads to inhibition. Menadione indirectly inhibits AKR7 via redox cycling, generating reactive oxygen species that oxidize important thiol groups, leading to the loss of enzymatic activity. Curcumin inhibits AKR7 by interfering with the active site and disrupting substrate interaction. Capsaicin can alter the conformation of AKR7 or interact with key residues necessary for activity, leading to inhibition. Nordihydroguaiaretic acid inhibits AKR7 either by competing with natural substrates at the active site or by modifying essential residues. Oleanolic acid can insert into the substrate binding site, blocking the processing of natural substrates and inhibiting the enzyme. Lastly, quercetin, a known flavonoid, can inhibit AKR7 by competing with coenzyme and substrate binding sites, effectively reducing the activity of the enzyme.