A Novel QSAR Platform to Identify Endocrine Disrupting Chemicals
There is a need for new approach methodologies to identify endocrine-disrupting chemicals (EDC) involved in key events of endocrine pathways notably binding to receptor proteins.
The industry will shortly be confronted with the obligations to test for potential endocrine modalities using a wide range of in vitro and in vivo methods under new REACH proposals while currently, in silico methods are not widely recognized and yet could greatly help in a widespread screening process.
The purpose of our research programme was to develop new, reliable, in silico methods which used together can accurately estimate the potential of chemicals for endocrine disruption. Two in-house tools have been developed: iSafeRat® ED SAR, a set of 2D structural alerts, and iSafeRat® SESAME-3D, a workflow for molecular docking. The 2D model was curated and validated using a diverse set of chemicals from the EPA Comptox and other databases. The docking workflow relies on third-party software for its major modeling stages and on an X-ray crystallographic dataset as input of protein targets. Its key features: automation and high-throughput, an open architecture allowing to build up consensus-problem-solving strategy. Currently using both our tools we are able to investigate a test ligand affinity for EATS target proteins. The Webinar will cover these two tools.
Speaker: Paul Thomas
Paul THOMAS has a Ph.D. in aquatic ecotoxicology and more than 20 years of experience with industrial chemicals, agrochemicals, and biocides gained initially at CIT (now Charles River) where he set up the ecotoxicology service and was study director for 4 years, ATOFINA (now ARKEMA) where he practiced ecotoxicology and Risk Assessment for existing substances and then AkzoNobel (now Nouryon) where he was head of the department, head of the ecotoxicology GLP and research laboratories and organiser of REACH services for the company for over 6 years. He joined CEHTRA in 2008 as director of CEHTRA Lyon specialising in REACH-related services and is the manager of the CEHTRA ecotoxicology team and contributed strongly to numerous successful registrations out of the >600 substances that CEHTRA registered since 2010 and has been working in the area of predictive ecotoxicology since this time. In 2014, while retaining all his roles in CEHTRA, Paul founded KREATiS and was nominated CEO KREATiS is a start-up company specialising in the creation of high accuracy QSARs to replace experimentation for REACH and other regulations. In 2020 he bought the company together with a human health expert, Dr. Carole Charmeau, and they have worked hard with the KREATiS team to bring the company to new heights, adding multiple models to their iSafeRat® model suite, and embracing new technologies such as 3D docking models for studying protein-ligand interactions.