Despite the fact that more than 50% of early stage of alzheimer's disease (ad) patients with mild cognitiveimpairment (mci) will progress to dementia within 5 years, current therapies provide minimal symptomaticrelief, without curing or halting disease progression. Phosphodiesterase-2a (pde2a), the most prevalent ofpdes expressed in the cortex, hippocampus and amygdala, regions involved in cognitive impairment, hasemerged as a promising target for the treatment of mild cognitive impairment without side effects. Despitepromising preclinical data showing that some inhibitors of pde2a inhibitors, such as bay 60-7550 and nd7001, enhance memory in animal models of ad, clinical studies have not advanced, due in part, to the lowselectivity, poor metabolic stability and brain penetrance of available compounds. The broad, long-term goal ofthis project is to discover and develop novel inhibitors of pde2a for the treatment of mci. To streamline theexciting project toward a clinical candidate, we have assembled a team with expertise in medicinal chemistryand drug discovery and pde-related pharmacology and pharmacokinetics. The complementary collaborationamong fd neurotechnologies (dr. Fu du), university at buffalo (drs. Ying xu and james m. O'donnell), anduniversity of arizona (dr. Wei wang) will synergize the effort by utilizing state-of-the-art drug discovery toolsand techniques to discover and optimize novel and drug-like inhibitors of pde2a and to evaluate theirpharmacological effects in cell and animal models. Research narratives
the goal of this project is to discover and develop safe, highly selective, and brain-penetrant pde2a inhibitors
with superior memory enhancing efficacy and potential to advance into clinical development for the treatment
of alzheimer's disease. 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phosphodiesterases ; plasma ; blood plasma ; plasma serum ; reticuloendothelial system, serum, plasma ;
