1 research outputs found
Exploring the Biologically Relevant Chemical Space for Drug Discovery
Both recent studies and our calculation
suggest that the physicochemical
properties of launched drugs changed continuously over the past decades.
Besides shifting of commonly used properties, the average biological
relevance (BR) and similarity to natural products (NPs) of launched
drugs decreased, reflecting the fact that current drug discovery deviated
away from NPs. To change the current situation characterized by high
investment but low productivity in drug discovery, efforts should
be made to improve the BR of the screening library and hunt drugs
more effectively in the biologically relevant chemical space. Additionally,
a multiple dimensional molecular descriptor, named the biologically
relevant spectrum (BRS) was proposed for quantitative structure–activity
relationships (QSAR) study or screening library preparation. Prediction
models for 43 biological activity categories were developed with BRS
and support vector machine (SVM). In most cases, the overall prediction
accuracies were around 95% and the Matthew’s correlation coefficients
(MCC) were over 0.8. Thirty-seven out of 48 drug-activity associations
were successfully predicted for drugs that launched from 2006 to 2012,
which were not included in the training data set. A web-server named
BioRel (http://ibi.hzau.edu.cn/biorel) was developed to
provide services including BR, BRS calculation, activity class, and
pharmacokinetic property prediction