Slide 1: Saying "I do" to the QSAR/PBPK marriage…
Saying “I do” to the QSAR/PBPK marriage… Goal: reliably and efficiently u<lize PBPK modeling to reduce animal/human tes<ng Permeability, solubility vs. pH, pKa(s), logD vs. pH, Fup, blood:plasma ra<o, <ssue Kps, CLint, CLfilt Quan<ta<ve Structure Ac<vity Rela<onships Physiologically-Based Pharmacokine<
Slide 2: Why is GastroPlus unique?
Why is GastroPlus unique? AbsorpEon & DissoluEon: • #1-ranked commercial QSAR models integrated • #1-ranked commercial model for absorp<on rate calcula<ons • Several dissolu<on models – including the popular Z-factor approach • Mechanis<c nuclea<on/growth precipita<on model • Paracellular permeabili
Slide 3: That's not all!
That’s not all! ANYTHING you can do with other tools can be done with GastroPlus: • Popula<on PBPK models (since 2005) • PBPK/PD modeling (since 2005) • DDI predic<ons (since 2008) • Mechanis<c IVIVCs (since 2001) • Nonlinear metabolism or transport kine<cs in any <ssue (since 2005) • … and more!
Slide 4: How do our model results compare?
How do our model results compare? Independent comparison of aqueous solubility predictors Comparison of first-in-human (FIH) PBPK predic<on accuracy in a 2-year study of 21 compounds (Dearden JC. Exper. Opin. Drug Discovery 2006 1:31) (Cole et al., ISSX 2008) Independent comparison of pKa predictors
Slide 5: Recent validation: The QSAR/PBPK marriage
Recent validaEon: The QSAR/PBPK marriage Daga et al. (2015) Gordon Research Conf. Lawless et al. (2015) ISSX Annual MeeEng Building QSAR models for clearance using 15-30 in Using QSAR & PBPK to predict human F%: vivo rat CL measurements: 70% of compounds predicted within 2-fold >75% of compounds pre
Slide 6: How does GastroPlus address your challenges?
How does GastroPlus address your challenges? Do I have the <me & exper<se to write code and No equa<on wri<ng AND customiza<on op<ons manage updates? available How do I define all of the parameters required for #1-rated QSAR models integrated for complete in a PBPK model? silico solu<ons What about o
Slide 7: Regulatory scientists trained on GastroPlus PBPK modeling
Regulatory scienEsts trained on GastroPlus PBPK modeling
Slide 8: Mission Statement
• In 2013, scien<sts from 17 companies in North America and Europe formed the GastroPlus User Group • To date, >930 members on the LinkedIn group page – membership is free! Mission Statement Discuss best prac<ces, Q&A and FAQs Present and advance M&S science via social media, webinars and face-to-fa