ATHL1 Inhibitors

ATHL1 inhibitors are chemicals that exert their effects through various mechanisms within the purine metabolic pathway, each leading to an indirect inhibition of ATHL1 activity. Allopurinol and Febuxostat are both xanthine oxidase inhibitors that would lead to the accumulation of purine metabolites, which can trigger feedback inhibition of ATHL1 by increasing the levels of substrates and intermediates that ATHL1 acts upon. Methotrexate and Sulfasalazine both inhibit the synthesis of purine and pyrimidine nucleotides; the resultant decrease in the availability of these molecules can lead to the indirect inhibition of ATHL1 due to a lack of substrates necessary for its action.

Mycophenolic acid, Ribavirin, Tiazofurin, and MIZORIBINE act as inosine monophosphate dehydrogenase inhibitors, which results in reduced guanosine nucleotide production. The consequent substrate depletion for ATHL1's purine-related functions can indirectly diminish its activity. Purine analogs like 6-Mercaptopurine, 6-Thioguanine, and Mercaptopurine Riboside mimic natural substrates of ATHL1 and can competitively inhibit the enzyme, leading to a decrease in its function. Azathioprine, a prodrug for 6-Mercaptopurine, similarly inhibits purine synthesis upon metabolism and thereby potentially reduces ATHL1 activity.