Otsuka Pharmaceutical Co developed tetomilast, a thiazole derivative for the treatment of inflammatory bowel disease and chronic obstructive pulmonary disease. Tetomilast acts as a selective inhibitor of phosphodiesterase-4 results in increased intracellular levels of cyclic adenosine monophosphate (cAMP), and subsequent anti-inflammatory effects. Specifically, the release of pro-inflammatory mediators including TNF-a and IL-12 is suppressed, and there is stimulation of the release of anti-inflammatory mediators including IL-10 and prostaglandin E2. Unfortunately, tetomilast clinical trials in patients with ulcerative colitis failed to demonstrate superior efficacy compared to mesalamine and further development of tetomilast was discontinued.