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1.  New classes of PDE7 inhibitors identified by a fission yeast-based HTS 
Journal of biomolecular screening  2010;15(4):359-367.
Studies of the phosphodiesterase PDE7 family are impeded by there being only one commercially-available PDE7 inhibitor, BRL50481. We have employed a high throughput screen of commercial chemical libraries, using a fission yeast-based assay, to identify PDE7 inhibitors that include steroids, podocarpanes, and an unusual heterocyclic compound, BC30. In vitro enzyme assays measuring the potency of BC30 and two podocarpanes, in comparison with BRL50481, produce data consistent with those from yeast-based assays. In other enzyme assays, BC30 stimulates the PDE4D catalytic domain, but not full-length PDE4D2, suggesting an allosteric site of action. BC30 significantly enhances the anti-inflammatory effect of the PDE4 inhibitor rolipram as measured by release of TNFα from activated monocytes. These studies introduce several new PDE7 inhibitors that may be excellent candidates for medicinal chemistry due to the requirements for drug-like characteristics placed on them by the nature of the yeast-based screen.
PMCID: PMC2854023  PMID: 20228279
Schizosaccharomyces pombe; cAMP; phosphodiesterase; high throughput; inhibitors; PDE7

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