ALKBH3 Inhibitors

The inhibitors of ALKBH3 (AlkB Homolog 3) encompass a diverse array of chemicals, each with distinct mechanisms of action. ALKBH3 is an enzyme involved in the oxidative demethylation of methylated nucleic acids, playing a crucial role in DNA repair and RNA metabolism. Due to its significance in these cellular processes, the inhibition of ALKBH3 can have profound implications on cellular function and genomic integrity. The inhibitors listed range from direct binders and competitive inhibitors to indirect modulators affecting the enzyme's activity or expression.

Direct inhibitors like Tranylcypromine and Methylstat interact with ALKBH3 at its active site. Tranylcypromine forms an irreversible bond, while Methylstat competes with the natural substrates of ALKBH3. These interactions disrupt the demethylation process, thereby inhibiting the enzyme's activity. Other inhibitors, such as IOX1 and N-Oxalylglycine, target the 2-oxoglutarate-dependent dioxygenase activity of ALKBH3. They mimic the substrate or compete with essential cofactors, thus impairing the catalytic function of ALKBH3. These mechanisms are crucial for regulating the enzyme's role in DNA and RNA processing. Indirect inhibitors like Dimethyl fumarate and Disulfiram modulate pathways that can influence the activity or expression of ALKBH3. Dimethyl fumarate works by altering oxidative stress pathways, which can impact DNA repair enzymes including ALKBH3. Disulfiram affects ALKBH3 indirectly through its action on acetaldehyde metabolism and oxidative stress modulation. Natural compounds such as Epigallocatechin gallate and Resveratrol have been suggested to impact ALKBH3 function through their broad antioxidative and anti-inflammatory properties, although their precise mechanisms in relation to ALKBH3 are less defined.