AKR1C20 Inhibitors

Chemical inhibitors of AKR1C20 can impede the protein's function by reducing the availability of its substrates, prostaglandins. Flufenamic acid, a fenamate group nonsteroidal anti-inflammatory drug (NSAID), can inhibit the protein by limiting the synthesis of prostaglandins via the inhibition of prostaglandin synthetase. Similarly, indomethacin, by inhibiting cyclooxygenase (COX), can decrease prostaglandin production and thus indirectly inhibit AKR1C20. Sulindac, through its active metabolites, inhibits both COX-1 and COX-2 enzymes, leading to a decrease in prostaglandin synthesis and a subsequent reduction in AKR1C20 activity due to a lack of substrate. Aspirin, which irreversibly inhibits COX enzymes, also results in decreased prostaglandin synthesis, further inhibiting AKR1C20 activity indirectly.

Continuing with the theme of COX inhibition, ibuprofen and naproxen both inhibit COX enzymes, which leads to reduced prostaglandin synthesis and thus a decrease in AKR1C20 activity. Ketoprofen adds to this list by similarly decreasing the synthesis of prostaglandins and therefore inhibiting AKR1C20. Piroxicam inhibits prostaglandin synthesis by blocking COX enzymes, again resulting in decreased AKR1C20 activity. Mefenamic acid, another fenamate group NSAID, inhibits COX and reduces prostaglandin synthesis, indirectly inhibiting AKR1C20. Diclofenac, known for potent COX inhibition, reduces prostaglandin synthesis and subsequently inhibits AKR1C20. Celecoxib, a selective COX-2 inhibitor, also reduces prostaglandin levels, inhibiting AKR1C20. Lastly, acetaminophen, primarily affecting COX-2 in the brain, reduces the synthesis of prostaglandins, thus limiting the activity of AKR1C20. All these chemicals share a common mechanism of reducing prostaglandin synthesis, which is crucial for AKR1C20 activity, thereby inhibiting the protein's function by decreasing the availability of its substrates.