Drug design at biological systems level
Remez Vinogradov, Nikita Nikita · LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) · 2016
The explosion of reductionist approaches at the end of the XXth century allowed for fast and high-throughput data collection in pharmaceutical industry, but did not deliver the expected gain in drug discovery performance. Omics methodologies were able to provide large amounts of information on one-to-one cause-effect relationships, but could not explain some of the complex effects in living organisms and biological systems in general. This Thesis, performed in the premises of an emerging biotech company, represents an attempt to explore the impact of an integrative systems approach to drug discovery. On the one hand, in silico prediction of drug-target interactions developed at Chemotargets was applied to the identifcation of cancer-relevant targets, the design of a biologically diverse chemical library, and the implementation of a novel methodology for predictive drug safety. On the other hand, major efforts were devoted to develop and carefully validate a new approach to anticipating in vivo organ toxicities from in vitro pharmacological profles and gene expression datas. This novel methodology was designed to complement and assist the expert toxicologist by providing insights at the anatomical level . Last but no least, key contributions have been made to develop a brand new platform-independent version of the company’s flagship software, CT-link, allowing for easy distribution and commercialization