Eric Martin,
Director, Computational Chemistry,
Novartis
Eric Martin has a Ph.D. in physical organic chemistry from Yale University. He has worked in computational drug design and herbicide design for over 30 years. Eric is best known for starting the now widely practiced field of combinatorial library design. He is currently developing novel methodologies for two areas of drug discovery: rational oral bioavailability design and protein-family virtual screening (PFVS). The former guides improvement of oral exposure during lead optimization by applying global sensitivity analysis to physiologically-based pharmacokinetics simulations (GSA of PBPK). PFVS computer models achieve accuracy comparable to experimental high throughput screening by combining all historical activity data from entire protein families, work for which Eric was awarded the lifetime title of Novartis Leading Scientist.
Rational Bioavailability Design: Global Sensitivity Analysis of Physiologically-Based Pharmacokinetics (GSA of PBPK)
Thursday, 29 September 2016 at 11:00
Add to Calendar ▼2016-09-29 11:00:002016-09-29 12:00:00Europe/LondonRational Bioavailability Design: Global Sensitivity Analysis of Physiologically-Based Pharmacokinetics (GSA of PBPK)In Silico Drug Discovery and Predictive Toxicology 2016 in San Diego, California, USASan Diego, California, USASELECTBIOenquiries@selectbiosciences.com
Medicinal chemists are eager for guidance on how to improve bioavailability (%F) for their compound series. From simple rules of thumb they can suggest over a dozen compound properties to adjust: solubility, logP, logD, Peff, CLint, PPB, RBP, MW, efflux, PSA, flexibility,pKa1, pKa2, pKb1, etc. Since the difficulty of multi-parameter optimization grows exponentially with the number of variables, efficient %F optimization requires identifying the 2 or 3 most influential properties for their specific medchem series. These very properties are also the principal inputs to physiologically-based pharmacokinetics (PBPK) models, which simulate the movement of a drug through an animal. Usually, PBPK simulations are carefully tuned for a few advanced drug candidates, using a combination of in vitro, in vivo and calculated inputs, to estimate human doses for clinical trials, or to prioritize compounds for expensive animal studies. In this work, GastroPlus PBPK models are instead customized for entire medchem series based on 15 to 20 rat PK studies. The key innovation was building a local QSAR for effective intrinsic clearance. All inputs are subsequently computed from structure alone, so the models can be applied to candidate molecules in advance of synthesis.
Add to Calendar ▼2016-09-29 00:00:002016-09-30 00:00:00Europe/LondonIn Silico Drug Discovery and Predictive Toxicology 2016In Silico Drug Discovery and Predictive Toxicology 2016 in San Diego, California, USASan Diego, California, USASELECTBIOenquiries@selectbiosciences.com
Add to Calendar ▼2016-09-29 11:00:002016-09-29 12:00:00Europe/LondonRational Bioavailability Design: Global Sensitivity Analysis of Physiologically-Based Pharmacokinetics (GSA of PBPK)In Silico Drug Discovery and Predictive Toxicology 2016 in San Diego, California, USASan Diego, California, USASELECTBIOenquiries@selectbiosciences.com
