Model-Free Drug-Likeness from Fragments

publication · 6 years ago
by Oleg Ursu, Tudor I. Oprea (University of New Mexico)
JChem Base
Rapid in silico selection of target focused libraries from commercial repositories is an attractive and cost-effective approach when starting new drug discovery projects. If structures of active compounds are available rapid 2D similarity search can be performed on multimillion compounds' databases. This in silico approach can be combined with physico-chemical parameter filtering based on the property space of the active compounds and 3D virtual screening if the structure of the target protein is available. A multi-step virtual screening procedure was developed and applied to select potential phosphodiesterase 5 (PDE5) inhibitors in real time. The combined 2D/3D in silico method resulted in the identification of 14 novel PDE5 inhibitors with <1 ╬╝MIC(50) values and the hit rate in the second in silico selection and in vitro screening round exceeded the 20%.
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