|
Short Courses | Day 1 | Day 2 | Day3 | Download Brochure Thursday, February 4
FRAGMENT-INSPIRED AND STRUCTURE-GUIDED MEDICINAL CHEMISTRY 8:25 AM Chairperson's Remarks Charles Reynolds, Ph.D., Research Fellow, Computer Aided Drug Discovery, Johnson & Johnson 8:30 Drug Discovery Facilitated by Fragment Screening Efforts
Rapid gain in potency of compounds by structure based drug design together with the high sensitivity of biophysical methods like Surface Plasmon Resonance (SPR) enable the use of fragment molecules to guide drug discovery efforts. The lecture will review the fragment screening efforts at Roche and analyze benefits and challenges of the approach from these experiences. Drug targets like β-secretase or chymase are used as case studies. 9:00 Synthesis, in vitro and in vivo Evaluation of PI3K Inhibitors Matthew Burger, Ph.D., Research Investigator II, Global Discovery Chemistry, Novartis Institutes for Biomedical Research Phosphoinositide-3-Kinase (PI3K) is an important oncology target due to the deregulation of its signaling pathway in a wide variety of human cancers. A lead series from a combinatorial library was identified that potently inhibits PI3K. Using SBDD the lead series was optimized to yield PI3K inhibitors with suitable PK properties to establish a PK/PD-efficacy relationship in a mouse A2780 xenograft model. 9:20 Design, Synthesis and Optimization 2-aminoquinazolines as PDK1 Inhibitors Savithri Ramurthy, Ph.D., Research Investigator, GDC/ONC, Novartis Institutes of Biomedical Research, Emeryville, CA Herein, we describe the use of iterative structure-guided design to discover two sets of leads from the series Quinazolines as PDK1 inhibitors. The in vitro and in vivo activity of potent PDK1 inhibitors will be discussed along with the medicinal chemistry approaches utilized to optimize the chemical series for kinase selectivity, efflux, and hERG. Sponsored by 
9:40 Fragment Based Drug Discovery at Evotec - Application to the identification of BACE and PDE10a inhibitors
10:30 Poster Competition Refreshment Break & Raffles in the Exhibit Hall 11:30 Computing Specific Residue-ligand Interaction Energies using Quantum Mechanical Energy Decomposition: A Tool for Guiding Drug Design Charles Reynolds, Ph.D., Research Fellow, Computer Aided Drug Discovery, Johnson & Johnson Quantum methods are just beginning to find wider application in drug discovery. We have used pair-wise decomposition of protein-ligand interaction energies, computed using the DivCon program, to analyze the interactions that drive potency in a series of protein kinase B inhibitors. These computed interaction energies were used to derive two heat maps: (1) an interaction energy map and (2) an SAR map.¦nbsp; These interaction energies, and resulting maps, provide detailed information not otherwise available for identifying the residues in an active site that are most critical for ligand binding. 12:00 PM The Emperor's New Crystal: Examples of X-ray Bloopers; a Cautionary Tale Edward Kesicki, Ph.D., Director, Small Molecule Drug Discovery, Infectious Disease Research Institute I will give examples of "solved" structures in which incorrect ligands were fitted to the electron density map of a kinase co-crystal, a result of a typographical error in the paperwork sent to the crystallographer. In addition, I will show a class of selective PI3 kinase inhibitors that would have never been discovered using known X-ray crystal structures. 12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own 1:45 Ice Cream Refreshment Break in the Exhibit Hall
PLENARY KEYNOTE SESSION 2:15 Plenary Keynote Introduction 2:25 Chips, Clones and Living Beyond 100
As information technologies and life sciences continue to converge, new business opportunities and challenges will arise for the field of diagnostics and beyond. This keynote reviews the deeper forces shaping the future of the biosciences, from social and economic to technological and political, including the stresses they will introduce for existing business models and healthcare. Not only will bioconvergence introduce new products, services and competitors, it may create entirely new industries on a scale larger than the computer revolution has to date. Several broad scenarios will be painted for the state of the biosciences in 2025 and the forces that might take us there, summarizing a multi-year strategy study conducted and supervised by the speaker at the Wharton school. 3:05 Refreshment Break in the Exhibit Hall
TARGETS IN HOT PURSUIT I 3:45 Chairperson's Remarks Thomas Höberg, Ph.D., Vice President, 7TM Pharma, Høsholm, Denmark 3:50 Redesign of Arylsulfonamide Gamma Secretase Inhibitors to Achieve Novelty and High in vivo Activity Andrei Konradi, Ph.D., Senior Director, Medicinal Chemistry, Elan Pharmaceuticals The transformation of known arylsulfonamide Gamma Secretase Inhibitors (GSIs) into Elan's arylsulfonyl pyrazolopiperidine GSIs, using small molecule modeling and pharmacophore hypotheses, will be described. Exploration of analogs to maximize in vitro potency, metabolic stability, pharmacokinetics, and in vivo activity will be presented. Several novel synthetic methods to prepare the target compounds will be described. 4:20 Discovery of the Nedd-8 Activating Enzyme Inhibitor MLN4924 Steve Langston, Ph.D., Senior Scientist, Millennium Pharmaceuticals, the Takeda Oncology Company The ubiquitin-proteasome system (UPS) is responsible for the regulated degradation of intracellular proteins with important roles in cellular function including cancer cell growth and survival. NEDD8-activating enzyme (NAE) is an essential component UPS that regulates degradation of a subset of proteins upstream of the proteasome. The discovery of MLN4924, a first in class inhibitor of NAE, will be presented. 4:50 Discovery of the Hedgehog Inhibitor GDC-0449 Michael Koehler, Ph.D., Scientist, Discovery Chemistry, Genentech, Inc. This talk describes the process by which a lead molecule, developed from a high-throughput screen, was re-scaffolded and optimized to become the systemic hedgehog pathway antagonist GDC-0449. It will include some structure-activity relationship work along with pre-clinical data and finally the initial clinical results in patients with metastatic basal cell carcinoma. 5:20 Exploration of SAR and optimization of in silico derived CRTH2 antagonists Thomas Höberg, Ph.D., Vice President, 7TM Pharma, Høsholm, Denmark Several chemical series of antagonists for the PGD2 receptor CRTH2 were identified from a small focused library originating from a knowledge-based process using physicogenetic relationships and ligand information. The elucidation of SAR by synthesis of smaller libraries and design of specific target structures led to identification of novel drugable chemotypes. 5:50 Close of Day
Short Courses | Day 1 | Day 2 | Day3 | Download Brochure |
Michael Henning, Ph.D., Vice Director & Head, Discovery
Technologies, F. Hoffmann-La Roche Ltd
Paul J.H. Schoemaker, Ph.D., M.B.A., Chairman and Chief Executive Officer,
Decision Strategies International, Inc.; Research Director, Mack Center for
Technological Innovation, The Wharton School; Adjunct Professor of Marketing,
The Wharton School Adjunct Professor, Wharton School of Business
|
|
 |