RDH9 Inhibitors

Chemical inhibitors of RDH9 include a variety of compounds that interact with the protein in different ways. Retinol directly competes with RDH9 for its substrate, retinaldehyde, thus inhibiting the enzyme's ability to reduce retinaldehyde to retinol. Citral, being an aldehyde itself, can act as an alternative substrate and therefore competes with the natural substrates of RDH9, effectively reducing its capacity to catalyze its intended reaction. Fomepizole works by binding to the active site of RDH9, which is also the binding site for alcohols, preventing the reduction of aldehydes to alcohols.

Stilbene oxide can inhibit RDH9 by binding to its active site or nearby allosteric sites, causing a conformational change that results in reduced enzymatic activity. Menadione may deplete the necessary cofactors required by RDH9 for its enzymatic function by acting as a substrate that is excessively reduced. Benzo[a]pyrene can form reactive intermediates that might bind to RDH9 and inhibit its function by forming adducts with the protein. Sulforaphane's inhibition mechanism involves the modification of thiol groups in or near the active site of RDH9, which can change the enzyme's conformation and inhibit its activity. Methanol competes for RDH9's active site as a competitive substrate, reducing the enzyme's ability to interact with its intended substrates. Pyrazole mimics the structure of RDH9's natural substrates and binds to the active site, thus inhibiting the protein. Lastly, Isotretinoin, known for its role in retinoid metabolism, can inhibit RDH9 by acting as a competitive inhibitor, utilizing the protein's role in the same metabolic pathway to exert its inhibitory effect.