jm7b00404_si_001.pdf (438.78 kB)
Fragment-Based Drug Discovery of Phosphodiesterase Inhibitors
Version 2 2017-08-11, 18:52
Version 1 2017-08-11, 15:44
journal contribution
posted on 2017-08-11, 18:52 authored by Fredrik Svensson, Andreas Bender, David BaileyPhosphodiesterases
are proving to be fruitful targets for drug
discovery. At the same time fragment-based drug discovery has matured
into a powerful and widely applied technique. In this communication
we review the application of fragment-based drug discovery for the
successful identification of novel 3′,5′-cyclic nucleotide
phosphodiesterase (PDE) inhibitors, concentrating on both experimental
and computational strategies for fragment screening and hit-to-lead
development. To this end, we also mine the open access databases ChEMBL
and PDB for fragments showing PDE inhibitory activity, as well as
SureChEMBL for recent PDE related patents, to provide a wider context
for exploring fragment diversity. Together these approaches form an
integrated experimental and computational platform to exploit fragment-based
drug discovery for this important gene superfamily.