Predictive QSAR modeling of phosphodiesterase 4 inhibitors.
A series of diverse organic compounds, phosphodiesterase type 4 (PDE-4) inhibitors, have been modeled using a QSAR-based approach. 48 QSAR models were compared by following the same procedure with different combinations of descriptors and machine learning methods. QSAR methodologies used random forests and associative neural networks. The predictive ability of the models was tested through leave-one-out cross-validation, giving a Q² = 0.66-0.78 for regression models and total accuracies Ac=0.85-0.91 for classification models. Predictions for the external evaluation sets obtained accuracies in the range of 0.82-0.88 (for active/inactive classifications) and Q² = 0.62-0.76 for regressions. The method showed itself to be a potential tool for estimation of IC₅₀ of new drug-like candidates at early stages of drug development.
Institute of Bioorganic Chemistry and Petrochemistry, National Academy of Sciences of Ukraine, Murmanska 1, Kyiv 9402660, Ukraine. vkovalishyn@yahoo.com
Vasyl
V
Kovalishyn
Vsevolod
V
Tanchuk
Larisa
L
Charochkina
Ivan
I
Semenuta
Volodymyr
V
Prokopenko
D001185:Artificial Intelligence; D003198:Computer Simulation; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4 / Q000737:chemistry*; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D016571:Neural Networks, Computer; D058988:Phosphodiesterase 4 Inhibitors / Q000737:chemistry*; D021281:Quantitative Structure-Activity Relationship
D058988:Phosphodiesterase 4 Inhibitors; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4