FMO9 Inhibitors

The chemical class referred to as FMO9 Inhibitors encompasses a range of compounds that interact with flavin-containing monooxygenases, a family of enzymes that include FMO9. These compounds are not necessarily exclusive to FMO9 but affect the enzyme through various interactions. One commonality among these inhibitors is their interaction with the FAD cofactor, a critical component required for the catalytic activity of FMOs. Binding to this cofactor, whether through covalent modification or non-covalent interaction, directly impacts the enzyme's ability to transfer oxygen from molecular oxygen to its substrate. Some inhibitors, such as methimazole and thiourea, effectively reduce the enzyme's activity through their action on the cofactor. Others, like tranylcypromine, form a covalent adduct with FAD, leading to sustained inhibition.

In addition to targeting the FAD cofactor, certain inhibitors, such as benzydamine and ketoconazole, can induce conformational changes in the enzyme that result in reduced substrate accessibility to the active site. This modality of inhibition underscores the flexibility and dynamism of the enzyme structure, which can be exploited by small molecules to decrease enzymatic activity. Furafylline and ticlopidine exemplify compounds that bind to the active site, directly competing with natural substrates and thus preventing the normal progression of the enzymatic reaction.