Hydrogen sulfide (H₂S) is a naturally occurring gasotransmitter with vasodilator and inflammatory modulating activity.^1,2 Non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, diclofenac, and ibuprofen, are some of the most commonly used anti-inflammatory drugs available but exhibit significant side effects, particularly gastric damage, when used chronically. ATB-337 is a hybrid molecule of an H₂S donor and the NSAID diclofenac.³ In rats, diclofenac at 10-50 µmol/kg caused significant gastrointestinal damage, whereas no damage was observed with ATB-337 treatment at the same dose. ATB-337 at 50 µmol/kg does not promote leukocyte adherence to vascular endothelium, an effect observed with diclofenac treatment alone. COX-1 and COX-2 were inhibited with similar efficacy by diclofenac and ABT-337. An increase in expression of the pro-inflammatory mediator TNF-α, as well as, the adhesion molecules ICAM-1 and LFA-1 were not observed in rats treated with 50 µmol/kg ABT-337, effects seen with equimolar doses of diclofenac. These results indicate that H₂S-releasing derivatives of NSAIDs may prove to be more effective anti-inflammatory agents than traditional NSAIDs alone.

1 Li, L., and Moore, P.K. Putative biological roles of hydrogen sulfide in health and disease: A breath of not so fresh air? Trends Pharmacol Sci 29(2) 84-90 (2007).

2 Wallace, J.L. Hydrogen sulfide-releasing anti-inflammatory drugs. Trends Pharmacol Sci 28(10) 501-505 (2007).

3 Wallace, J.L., Caliendo, G., Santagada, V., et al. Gastrointestinal safety and anti-inflammatory effects of a hydrogen sulfide-releasing diclofenac derivative in the rat. Gastroenterology 132 261-271 (2007).

Wallace, J.L. Hydrogen sulfide-releasing anti-inflammatory drugs. Trends Pharmacol Sci 28(10) 501-505 (2007).

Wallace, J.L., Caliendo, G., Santagada, V., et al. Gastrointestinal safety and anti-inflammatory effects of a hydrogen sulfide-releasing diclofenac derivative in the rat. Gastroenterology 132 261-271 (2007).

Li, L., and Moore, P.K. Putative biological roles of hydrogen sulfide in health and disease: A breath of not so fresh air? Trends Pharmacol Sci 29(2) 84-90 (2007).

ATB-337 is available in the following screening library:

• Bio-active Lipid I Screening Library (96-Well)