ACY1L2 Inhibitors

Chemical inhibitors of Acylase 1-like 2 (ACY1L2) encompass a diverse range of compounds that interact with the enzyme's activity through various indirect mechanisms. Acetazolamide, by inhibiting carbonic anhydrase, alters the balance of carbonic acid and bicarbonate in cells, which can affect the pH-dependent conformation of ACY1L2. This alteration in pH can alter the enzyme's activity, impacting its ability to hydrolyze its specific substrates. Methotrexate, through its inhibition of dihydrofolate reductase, leads to a decrease in tetrahydrofolate, which is crucial for purine nucleotide biosynthesis and amino acid metabolism. This disruption can lead to an accumulation of certain amino acids or peptides, which in turn can influence the activity of ACY1L2. Triclosan inhibits fatty acid synthesis, affecting the lipid composition of membranes and potentially disrupting the optimal lipid environment necessary for ACY1L2's activity. Clomiphene, as a selective estrogen receptor modulator, can induce hormonal changes that may influence the expression levels or the availability of substrates and cofactors for ACY1L2.

Furthermore, Disulfiram, by inhibiting aldehyde dehydrogenase, increases acetaldehyde concentration, which can modify the catalytic activity of ACY1L2. The pyrimidine analog 5-Fluorouracil disrupts DNA synthesis, potentially affecting protein and peptide turnover or metabolic pathways that provide substrates for ACY1L2. Omeprazole's irreversible inhibition of H+/K+ ATPase leads to changes in gastric pH levels, which can affect the systemic pH and thus ACY1L2's activity. The tyrosine kinase inhibitor Imatinib can alter phosphorylation patterns within the cell, potentially impacting ACY1L2's stability or activity. Azathioprine, after being metabolized into mercaptopurine, inhibits purine synthesis, which can alter the balance of metabolic intermediates necessary for ACY1L2's function. Aminoguanidine's inhibition of nitric oxide synthase and formation of advanced glycation end-products can modify the cellular environment, impacting ACY1L2's structure and function. Lovastatin's inhibition of HMG-CoA reductase affects cholesterol synthesis and thus membrane fluidity, potentially altering ACY1L2's localization or interactions within the cell membrane. Lastly, Tetracycline, by inhibiting bacterial protein synthesis, can affect the production of bacterial metabolites that normally interact with ACY1L2.