UK-500001

UK-500001 is a small molecule phosphodiesterase 4 (PDE4) inhibitor that was developed by Pfizer as an inhaled anti-inflammatory agent for the maintenance treatment of chronic obstructive pulmonary disease (COPD)[1][6][7]. It is an isoform-selective but subtype-nonselective PDE4 inhibitor with nanomolar potency against several PDE4 subtypes (IC50 values: PDE4A 1.9 nM, PDE4B 1.01 nM, and PDE4D 3.78 nM)[6]. The drug was designed to be administered as a dry powder for inhalation to maximize local efficacy in the lungs while minimizing systemic side effects commonly associated with oral PDE4 inhibitors[6][7]. Preclinical studies demonstrated robust anti-inflammatory activity and inhibition of TNF-alpha and IFN-gamma release in human and rodent macrophage cell lines[2], as well as efficacy in animal models of airway inflammation[6][7]. However, clinical trials in patients with moderate to severe COPD failed to demonstrate significant efficacy at any dose tested; additionally, systemic side effects such as diarrhea were observed despite the intended lung-targeted delivery[7]. As a result of these findings, development was discontinued after phase II trials[5][7].

Other names

2-(3,4-difluorophenoxy)-5-fluoro-N-[(1s,4s)-4-(2-hydroxy-5-methylbenzamido)cyclohexyl]pyridine-3-carboxamide