Target Analysis - Purinoreceptors
P2Y2 and the future of purinoreceptors
Inspire Pharmaceuticals is a company with a strong presence in P2Y2 receptor drug discovery, based on technology licensed from the University of North Carolina (UNC), the US. Researchers working at UNC's Cystic Fibrosis Research Center discovered that UTP improved mucociliary clearance and increased surface airway hydration. Inspire Pharmaceuticals currently has two P2Y2 agonists under development: denufosol tetrasodium, in Phase III clinical trials for cystic fibrosis and diquafosol tetrasodium, which has finished trials and is awaiting approval in Japan and the US for Sjogren's syndrome and dry-eye syndrome, respectively. In pivotal Phase III trials, denufosol tetrasodium provided significant improvement over placebo in the primary endpoint of the study and was safe and well tolerated. Diquafosol tetrasodium failed to meet its primary endpoint in an FDA-requested Phase III trial to confirm efficacy. Inspire plans to initiate a further Phase III trial under a Special Protocol Assessment from the FDA after validating clinical endpoints in dry-eye studies. The only other P2Y2 receptor-targeted drug in active development is EPIX Pharmaceuticals' EPX-16006, an orally-available agonist, for the treatment of IBS. It stimulates chloride ion secretion in the GI tract, and has been shown to improve GI motility in preclinical studies.
Much of the research on P2 purinoreceptors has been carried over the previous 15 years and it is expected that these important receptors will be implicated in the pathology of more disorders. The ubiquitous expression of the receptors many tissues makes the future of purinoreceptor research unpredictable but exciting. The first P2 receptor antagonists (ticlopidine and clopidogrel) were products of traditional drug discovery and were first launched in 1978 and 1998 respectively . With the first of the new wave of P2 purinoreceptor drugs now awaiting approval, it remains to be seen if these new candidates can mimic the commercial success of these drugs. With the steep increase in the number of P2 purinoreceptor- targeted drugs in development over the past 13 years (Graph 2) expected to continue, the future of this class drugs does indeed look promising.
Mohamed Farah
Pharmaprojects Analyst
Image courtesy of Trounce under the Creative Commons Attribution ShareAlike 2.5 License
