NovaMecahanics' published a predicting QSAR workflow for the in silico identification and screening of novel HDAC inhibitors

January 2009

In this work (Molecular Diversity  doi:10.1007/s11030-009-9115-2), a series of 58 5-pyridin-2-yl-thiophene-2-hydroxamic acids with HDAC inhibitory activity, recently discovered by Argenta Discovery Ltd was studied . First, a quantitative structure – activity relationship was explored with 69 different physicochemical, topological and structural descriptors being considered as inputs to the model. Among different candidates, a linear five-parameter QSAR model was selected as the most accurate and reliable using a rigorous and systematic variable selection method. A virtual screening study was then conducted to identify novel biologically active patterns by insertion, deletion and substitution of different substitutes of the original molecules. The study led to the identification of novel structures, which are potent HDAC inhibitors according to the QSAR model. The structures were filtered using the domain of applicability of the QSAR model. In summary, novel structural scaffolds were found using QSAR predictive workflow  combined with synthetic chemistry knowledge in order to ensure that the novel scaffolds projects are chemistry driven. This in silico screen based on a simple QSAR model clearly achieved its objective in identifying compounds with improved predicted activity while simultaneously identifying structural modifications that were deemed out of the domain of applicability and therefore the scope of the models reliability. The in silico screen thus demonstrates the usefulness of constructing QSAR models which can act as aids in identifying new synthetic targets for drug discovery. (Full article available via Springer)

NovaMechanics’  published the first QSAR study concerning antagonists of CXCR3 in the literature

 June 2008

NovaMechanics, Fleming's and NTUA's researchers have used molecular modeling and cheminformatics methods to derive relationships between chemical structure and biological activity of small-molecule antagonists of the CXCR3 receptor, a drug development target for chronic inflammatory diseases. The authors' in silico model (which is the first QSAR study concerning antagonists of CXCR3 in the literature) provides a time- and cost-effective tool for screening existing and virtual libraries of small molecules as well as for designing of novel molecules of desired activity. (Full article available via Sciencedirect)