Mastering Medicinal Chemistry

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Wednesday, February 3

7:00 AM Registration and Morning Coffee

8:10 When Drug Research is Personal

John F. Crowley, Founder, Novazyme Pharmaceuticals, Inc.

Mr. Crowley's emotion-packed presentation will focus on his personal struggle to find a cure for Pompe disease, a rare and fatal illness that is caused by a defective or missing enzyme. Pompe disease affects fewer than 10,000 people world-wide, including Mr. Crowley's two small children. Mr. Crowley, a Harvard educated businessman, created and built a pharmaceutical company devoted expressly to finding a cure for the disease. He will detail his journey through the labyrinth of scientific and business fronts, which lead up to a first-round clinical trial.

8:55 Technology, Aging, and the Brain

Gary W. Small, M.D., Parlow-Solomon Professor on Aging, Professor of Psychiatry & Biobehavioral Sciences, Director, UCLA Center on Aging, Director, Memory & Aging Research Center, Director, Geriatric Psychiatry Division, Semel Institute for Neuroscience & Human Behavior, David Geffen School of Medicine at UCLA

New neuroimaging and other technologies are teaching us about how the brain ages and what we can do about it. Although memory declines as we age, medical and nonpharmacological strategies may protect brain health and improve memory performance. At the same time, innovation in digital technology is not only changing the way we live and communicate, it appears to be altering how our brains function. As a consequence of this high-tech stimulation, we are witnessing the beginning of a new form of the generation gap - a brain gap dividing younger digital natives, immersed in the technology early in life, from older digital immigrants, who adapt to the new technology more reluctantly. This lecture will describe this current pivotal point in brain evolution and how we can harness the new technology and lifestyle choices to improve memory and brain function so we can live better and longer.

9:40 Grand Opening Refreshment Break in the Exhibit Hall

KEYNOTE PRESENTATIONS:
RECENT APPROVALS AND CLINICAL CANDIDATES

11:00 Chairperson's Remarks

Hing Sham, Ph.D., Senior Vice President, Chemical Sciences, Elan Pharmaceuticals

11:10 Recent Approval: Mozobil from Development to Approval

Renato Skerlj, Ph.D., VP, Medicinal Chemistry, Genzyme Corporation Drug and Biomaterial R&D

Mozobil(TM) (plerixafor injection), a first in class small molecule antagonist of the chemokine receptor CXCR4, was granted marketing approval by the FDA in December 2008 and indicated for the mobilization of hematopoietic stem cells to the bloodstream for collection and subsequent autologous transplantation in patients with non-Hodgkin's lymphoma and multiple myeloma.

11:40 Discovery of a State-Dependent Cav2.2 Blocker for the Treatment of Chronic Pain

Scott B. Hoyt, Ph.D., Research Fellow, Department of Basic Chemistry, Merck Research Laboratories

Voltage-gated Cav2.2 calcium channels control the release of neurotransmitter at presynaptic terminals, and thus play a critical role in pain signaling. The state-independent Cav2.2 blocker ziconotide, a peptide that must be administered via intrathecal injection, has demonstrated clinical efficacy in the treatment of severe chronic pain. State-dependent Cav2.2 blockers may likewise provide clinical pain relief without adversely affecting other nerve functions.

12:10 PM Discovery of Lorcaserin: A Selective 5-HT2C Agonist for the Treatment of Obesity

Brian Smith, Ph.D., Director, Medicinal Chemistry, Arena Pharmaceuticals, Inc.

Compelling evidence suggests that drugs which activate the 5-HT2C receptor cause weight loss and thus have potential as anti-obesity agents. Because serotonin elicits a number of biological responses through modulation of other 5HT receptors, selectivity has been a critical challenge. This presentation outlines events, challenges and achievements that led to the discovery and development of lorcaserin.

12:40 Luncheon Presentation (Sponsorship Opportunity Available) or Lunch on Your Own

1:45 Dessert in the Exhibit Hall

CASE STUDIES FROM CHEMISTRY TO THE CLINIC

2:15 Chairperson's Remarks

2:20 Discovery of SCH 530348 - A Thrombin Receptor Antagonist with Potent Antiplatelet Effects

Samuel Chackalamannil, Ph.D., Distinguished Research Fellow, Discovery Research, Schering-Plough Research Institute

SCH 530348, a himbacine-based thrombin receptor antagonist (TRA), is currently undergoing Phase-III clinical studies for acute coronary syndrome and secondary prevention of cardiovascular events in high risk patients. In a Phase-II clinical study in PCI patients, SCH 530348 showed no statistically significant increase in major or minor bleeding when added to standard of care, and showed a non-statistically significant reduction in major adverse cardiac events, including periprocedural myocardial infarction.

2:50 Macrocycle-based Drug Discovery: The Ulimorelin Story

Helmut Thomas, Ph.D., Senior Vice President, Research & Preclinical Development, Tranzyme Pharma, Inc.

The discovery and development path leading from a small molecule macrocyclic screening library to the novel ghrelin receptor agonist, ulimorelin (TZP-101), a Phase III product for the treatment of GI hypo-motility disorders, will be presented in detail. The specific attributes of the medicinal chemistry technology (MATCH (TM)) that enabled the rapid progression of these efforts from hit-to-lead-to-clinic will be outlined.

3:20 Executive Panel

Medicinal Chemistry Drivers: Innovation, Technology, Efficiency and Luck

Moderator: Graeme Semple, Ph.D., Vice President, Discovery Chemistry, Arena Pharmaceuticals, Inc.

Panelists:

Michael Henning, Ph.D., Vice Director & Head, Discovery Technologies, F. Hoffmann-La Roche Ltd

Andrei Konradi, Ph.D., Senior Director, Medicinal Chemistry, Elan Pharmaceuticals

Kenneth A. Savin, Ph.D., Manager, Global External Research & Development, Eli Lilly & Co.

Gary W. Small, M.D., Parlow-Solomon Professor on Aging, Professor of Psychiatry & Biobehavioral Sciences, Director, UCLA Center on Aging

3:50 Thermodynamic Contributions of Water Molecules to Ligand-Receptor Binding
Christopher Higgs, Ph.D., MRSC, Senior Applications Scientist, Schrödinger, LLC
Interpreting structure-activity data is often challenging even with the availability of
crystal structures. The role of solvent thermodynamics in protein binding sites is often
overlooked but can be important in explaining experimental data. Here, we present a
statistical thermodynamic approach to the treatment of binding site water molecules and
show that hydration site displacement patterns can be used to explain SAR trends, ligand
selectivity, and site-directed mutagenesis. Applications of the method to the A2A
adenosine receptor, PDZ domains, a broad range of kinases, and other systems of
pharmaceutical interest will be discussed.