Biology subjects

Gaulton, A.

Publications and source records attributed to Gaulton, A..

3 recordsLinked to original sources

bioRxiv2022

Illuminating the Druggable Genome through Patent Bioactivity Data

The patent literature is a potentially valuable source of bioactivity data. The SureChEMBL database (https://www.surechembl.org/) is a publicly available large-scale resource that contains compounds extracted on a daily basis from the full text, images and attachments of patent documents, through an automated text and image-mining pipeline. In this paper we describe a process to prioritise 3.7 million life science relevant patents obtained from SureChEMBL, according to how likely they were to contain bioactivity data for potent small molecules on less-studied targets, according to the classification developed by the Illuminating the Druggable Genome (IDG) project. The overall goal was to select a smaller number of patents that could be manually curated and incorporated into the ChEMBL database. We describe the approach taken, the results obtained, and provide some illustrative examples.

bioinformatics↗

bioRxiv2020

Validation of lipid-related therapeutic targets for coronary heart disease prevention using human genetics

Drug target Mendelian randomization (MR) studies use DNA sequence variants in or near a gene encoding a drug target, that alter its expression or function, as a tool to anticipate the effect of drug action on the same target. Here, we applied MR to prioritize drug targets for their causal relevance for coronary heart disease (CHD). The targets were further prioritized using genetic co-localization, protein expression profiles from the Human Protein Atlas and, for targets with a licensed drug or an agent in clinical development, by sourcing data from the British National Formulary and clinicaltrials.gov. Out of the 341 drug targets identified through their association with circulating blood lipids (HDL-C, LDL-C and triglycerides), we were able to robustly prioritize 30 targets that might elicit beneficial treatment effects in the prevention or treatment of CHD. The prioritized list included NPC1L1 and PCSK9, the targets of licensed drugs whose efficacy has been already proven in clinical trials. To conclude, we discuss how this approach can be generalized to other targets, disease biomarkers and clinical end-points to help prioritize and validate targets during the drug development process. One Sentence SummaryWe provide genetic support for lipid-modifying drug targets for coronary heart disease prevention using drug target Mendelian randomization and further prioritization based on clinical and biological evidence.

genetics↗

bioRxiv2017

Flipping the odds of drug development success through human genomics

Drug development depends on accurately identifying molecular targets that both play a causal role in a disease and are amenable to pharmacological action by small molecule drugs or bio-therapeutics, such as monoclonal antibodies.\n\nErrors in drug target specification contribute to the extremely high rates of drug development failure.\n\nIntegrating knowledge of genes that encode druggable targets with those that influence susceptibility to common disease has the potential to radically improve the probability of drug development success.

genomics↗