GSK356278 / GSK - LARVOL DELTA

Pharmacophore-driven design and biological evaluation of heterocyclic PDE4B inhibitors for Alzheimer's disease. (PubMed, RSC Adv) - "GSK356278 and Rolipram are the known PDE4B modulators, which have been considered for the current study to generate significant pharmacophoric features and execute drug design as CNS-active PDE4B inhibitors...PC12 cell lines were chosen to verify the in vitro neuroprotective response, and the Drosophila model for in vivo for AD assessment. All of these results indicated the significance of pyridine-based heterocycles molecules as potential candidates for PDE4B-targeted AD treatment."

Journal • Alzheimer's Disease • CNS Disorders • Inflammation

Inhibition of hippocampal mossy fiber plasticity and episodic memory by human Aβ oligomers is prevented by enhancing cAMP signaling in Alzheimer's mice. (PubMed, Alzheimers Dement) - "Early episodic memory deficits in AD linked to oAβ-induced synaptic dysfunction. Isoproterenol and GSK356278 improve mossy fiber-LTP and fear memory deficits. FLIM-FRET shows treatments restore cAMP signaling in dentate gyrus neurons. Isoproterenol reduces synapsin I hyperphosphorylation and microgliosis. Enhancing cAMP signaling may help mitigate early memory deficits in AD."

Journal • Preclinical • Alzheimer's Disease • CNS Disorders • CA3

Quantification of human brain PDE4 occupancy by GSK356278: A [(11)C](R)-rolipram PET study. (PubMed, J Cereb Blood Flow Metab) - "We present the first report of a direct estimation of PDE4 blockade in the living human brain. In vivo affinity of GSK356278 for the PDE4, estimated in this early phase study, was combined with GSK356278 safety and tolerability data to decide on a therapeutic dose for future clinical development."

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