no-indomethacin

NO-indomethacin is a hybrid molecule of indomethacin and a nitric oxide (NO) donor. This drug design combines the anti-inflammatory properties of a non-steroidal anti-inflammatory drug (NSAID) with the gastrointestinal protective effects of NO. Compounds of this class retain their anti-inflammatory and analgesic activity, but have reduced gastrointestinal and kidney toxicity compared to the NSAID alone. NO-indomethacin also enhances the cancer chemopreventative activity of indomethacin. NO-indomethacin exhibits an IC50 of 82 μM, compared to >1,000 μM for indomethacin alone, for the inhibition of pancreatic cancer cell (PaCa-2) growth after 24 hours in culture.

COX-2-IN-51 (E25) is a potent COX-2 inhibitor with an IC50 of 70.7 nM. It significantly suppresses LPS-induced release of NO and PGE2, the expression of COX-2 and iNOS, and the activation of the NF-κB pathway. Displaying anti-inflammatory and analgesic effects in various mouse models through NF-κB pathway inhibition, COX-2-IN-51 has lower gastrointestinal side effects compared to Indomethacin.

Tinoridine hydrochloride (Y-3642 hydrochloride) is a non-steroidal anti-inflammatory drug. Tinoridine hydrochloride (5-100 μM), produced a concentration-dependent inhibition on the simultaneous increases in lipid peroxide formation and renin release induced by 50 μM ascorbic acid in the renin granule fraction. On the other hand, indomethacin, hydrocortisone, and prednisolone, which had no ability to inhibit the lipid peroxidation in the renin granule fraction, did not influence the release of renin from the granules. These results suggest that tinoridine suppresses renin release by inhibiting the oxidative disintegration of membranes of renin granules.