PRE-CONFERENCE SHORT COURSES:APRIL 15
Monday, April 15 • 8:00-11:00 am
Molecular Interactions and Drug Design
Instructors: Kent Stewart, Ph.D., Senior Research Fellow, AbbVie
This course provides an overview of protein-ligand interactions and drug design principles. The presentation is targeted to medicinal chemists. Part 1 covers hydrophobic, H-bonding and electrostatic interactions; Part 2 covers specialized topics such as conformation analysis, pi-stack, cation-pi, halogen bonding, protein-protein interface, and covalent inhibition. Med chem case studies are incorporated.
- Learn drug design principles generally applicable to all med chem programs.
- Interpret atomic-level protein X-ray and modeled structures of binding modes.
- Understand the relative amounts of potency gain from different interactions.
- Case studies illustrate all of the design strategies.
Kent Stewart, Ph.D., Senior Research Fellow, AbbVie
Dr. Stewart has over 27 years experience in drug discovery and more than 90 research publications. Contributed to 8 candidate compounds, with one in advanced clinical evaluation. Specialist in computer-aided drug design. Ph.D. in Organic Chemistry from University of California, Los Angeles, and post-doctoral work in biochemistry at the Rockefeller University.
An Intro to the Field of Antibody-Drug Conjugates
Instructor: Ho Sung Cho, Ph.D., Chief Technology Officer, Ambrx
ADCs are an emerging modality in cancer. This course will give you an overview of the current advances being made in the clinic, review the design of novel payloads and linkers, and discuss some of the challenges being faced in developing future linkers and cytotoxic drugs.
- Design of novel linkers, payloads and ADCs for Cancer
- Innovative chemistry strategies for ADC discovery
- Design, synthesis, and characterization of small molecule antibody therapeutics
Dr. Ho Sung Cho is the Chief Technology Officer of Ambrx. He has over 22 years of experience in recombinant protein engineering, expression, purification, modification, and analysis. Prior to joining industry, Dr. Cho was a staff scientist at Lawrence Berkeley National Labs where he worked on the structural genomics project. He received his B.S. in Chemistry from North Carolina State University and his Ph.D. in Chemistry from the University of California at Berkeley.
Monday, April 15 • 12:00 - 3:00 pm
Advancing Tools and Technologies for Fragment-Based Design
Instructors: Daniel A. Erlanson, Ph.D., Co-Founder, Carmot Therapeutics, Inc.
Edward R. Zartler, Ph.D., President & CSO, Quantum Tessera Consulting
Part 1: Concepts, Challenges, and Applications of FBDD
- Why fragments?
- Pitfalls to finding fragments
- What makes a good fragment?
- What to do with a fragment – growing, linking, and more
Part 2: The practical issues of FBDD
- Design of fragment libraries and how big should a library be?
- Overview of potential screening methods – advantages and disadvantages
- How do you choose the best method for your target?
- Importance of using orthogonal/multiple methods
Dr. Daniel A. Erlanson is the co-founder of Carmot Therapeutics, Inc. (http://www.carmot.us), a small-molecule drug discovery company applying fragment-based approaches to a variety of therapeutic targets. Prior to Carmot, Dr. Erlanson spent a decade developing fragment-based drug discovery technologies at Sunesis Pharmaceuticals, which he joined at the company's inception. Before Sunesis, he was an NIH postdoctoral fellow with James A. Wells at Genentech. Dr. Erlanson earned his PhD in chemistry from Harvard University in the laboratory of Gregory L. Verdine and his BA in chemistry from Carleton College. As well as co-editing the first book on fragment-based drug discovery, Dr. Erlanson is an inventor on more than a dozen issued patents and published patent applications and an author of more than two dozen scientific publications. He is also editor in chief of Practical Fragments (http://practicalfragments.blogspot.com/), a blog devoted to fragment-based drug discovery.
Dr. Edward R. Zartler is the Chief Scientific Officer of Quantum Tessera Consulting (www.quantumtessera.com). Dr. Zartler works with clients developing practical applications of Fragments and biophysical methods leveraging his decade in the pharmaceutical industry (at Merck and Eli Lilly). While at Eli Lilly, Dr. Zartler implemented and led all fragment efforts there and coined the term "Fragonomics." Prior to joining Lilly, Dr. Zartler did his post-doctoral training with James Prestegard at the University of Georgia. He earned his Ph.D. from the University of Pennsylvania under Ponzy Lu and his B.A. in Chemistry from Goucher College. Dr. Zartler is co-editor of the second book on Fragment-based Drug Discovery. He is also editor of Practical Fragments (with Dr. Erlanson) (http://practicalfragments.blogspot.com/), a blog devoted to fragment-based drug discovery.
Immunology Basics for Chemists
Instructor: Kenneth C. Kalunian, M.D., Professor of Clinical Medicine, Rheumatology in Department of Medicine, University of California San Diego Medical School
Topics to be covered:
Review of inflammatory processes
- Cytokine biology
- Receptor pathways
Autoimmune and inflammation-related diseases
- Which are most prevalent? which have the greatest need for new therapies?
- Underlying biologic defects
- Associated targets and their place in signal transduction pathways
Current treatment landscape
- Review of current state of anti-cytokine therapies (mostly biologics)
- Biologics v. small molecules
- What's on the horizon
- What is needed
Dr. Kalunian is well suited for leading a course on Immunology Basics for Chemists because his medical focus is on autoimmune-related diseases – both from a basic research and clinical medicine perspective. He also has a fundamental background in chemistry from his undergraduate training. His research focuses on innovative strategies for the treatment of patients with rheumatoid arthritis and other rheumatic diseases. His work is also aimed at uncovering prognostic and predictive factors for outcomes in rheumatic diseases. Dr. Kalunian treats patients with lupus, osteoarthritis and rheumatoid arthritis in his clinical practice. Dr. Kalunian received his AB in chemistry at Occidental College in Los Angeles, CA. He earned his MD at St. Louis University Medical School in St. Louis, MO.
Monday, April 15 • 3:30 - 6:30 pm
Enabling Macrocyclic Compounds for Drug Discovery: Opportunities, Challenges and Strategies
Instructors: Mark L. Peterson, Ph.D., Vice President, IP & Operations, Tranzyme Pharma
Macrocyclic compounds fill an important chemical space between small molecules and biologics. This course will discuss the recent developments in the field of macrocycle synthesis and screening, as well as specific aspects of these compounds for drug discovery and development purposes.
- Unique characteristics of macrocycles
- The challenges of macrocycle synthesis and screening
- Current methods for synthesizing and screening macrocyclic compound libraries
- Pros and cons of each methodology
- Drug discovery and development considerations for macrocyclic molecules
- Examples in the discovery of bioactive synthetic macrocycles
- Remaining challenges and possible solutions
Dr. Peterson is currently Vice President, IP & Operations at Tranzyme Pharma. He was previously with Monsanto and Advanced ChemTech, where he worked in a wide variety of research areas including structure-based design, solid phase organic chemistry, combinatorial libraries, synthesis automation, heterocycles, unnatural amino acids, peptides and peptidomimetics. With Tranzyme Pharma since 1999, Dr. Peterson led the chemistry R & D efforts during the technology development stage of the company and the initiation of its drug discovery programs before assuming his present position in 2003. A native of Wisconsin, he received his Ph.D. in Organic Chemistry from Washington State University and conducted post-doctoral research at the University of Minnesota prior to starting his industrial career. He is author or co-author of over 80 publications and abstracted presentations plus two book chapters, as well as co-inventor on over 20 patents.
Introduction to Allosteric Modulation of GPCRs
Instructor: Karen J. Gregory, Ph.D., Post-Doctoral Fellow, Jeffrey Conn Laboratory, Pharmacology, Vanderbilt University
Quantifying allosteric modulation
- Binding vs functional assays
- HTS and in vitro strategies
- In vivo experimental design
Complexities and challenges
- What to optimize for?
- Molecular switches and flat/steep SAR
- Modulation bias & context dependent pharmacology
- Multiple allosteric sites
- Probe dependence
- Some GPCRs are functional heterodimers
How can structural information aid modulator drug discovery?
- Mechanism validation (orthosteric, allosteric or bitopic?)
- Inform SAR
- Identify novel binding sites
- >Virtual ligand screening
Karen J. Gregory, Ph.D., Post-Doctoral Fellow, Jeffrey Conn Laboratory, Pharmacology, Vanderbilt University
Karen Gregory, Ph.D., is a postdoctoral research fellow who joined Jeffrey Conn's laboratory in August 2009. As a recipient of the prestigious Dowd Foundation (Neuroscience) and NHMRC (Australia) Dora Lush postgraduate research scholarships she undertook her doctoral training in the laboratories of Profs. Arthur Christopoulos and Patrick Sexton at Monash University in Melbourne, Australia. During her Ph.D., Karen investigated the functional consequences of allosteric modulation of M2 muscarinic acetylcholine receptors.
In the Conn laboratory, Dr. Gregory continues to pursue her interest in G protein-coupled receptor (GPCR) pharmacology focusing on metabotropic glutamate receptor 5 (mGlu5). Dr. Gregory investigates the structural determinants that underlie allosteric ligand binding to mGlu5 with the aim of facilitating rational drug design efforts. Dr. Gregory received her undergraduate degree in Pharmacology from The University of Melbourne and earned her Ph.D. in Pharmacology from Monash University.
DINNER SHORT COURSES:APRIL 17
Wednesday, April 17 Dinner Courses • 6:30 - 9:00 pm
Practical Aspects of Structure-Based Drug Discovery with GPCRs
Instructors: Robert Cooke, Ph.D., Head, Biomolecular Structure Department, Heptares
Michael Hanson, Ph.D., Director, Structural Biology, Receptos
- The quality of structures that can be expected and what can be done with the data
- Expected throughput and turnaround times
- Working with fragments
- Dealing with conformational states
- Impact on modeling activities
- Comparison with more established SBDD efforts (eg kinases)
- >Incorporating data from purified protein assays
- A couple of case studies covering the process
Robert Cooke, Ph.D., Head, Biomolecular Structure Department, Heptares
Robert Cooke, Ph.D., obtained his BSc and Ph.D. (Inorganic Chemistry) from the University of Sydney. He then did post-doc studies with Iain Campbell in the Department of Biochemistry at University of Oxford determining solution structures of growth factors by NMR. Rob joined Glaxo to establish protein NMR studies, and while at Glaxo, Glaxo Wellcome and Glaxo Smith Kline he led a number of areas including structural biology & biophysics, protein production, analytical chemistry and biochemistry, and computational chemistry. Rob has also been involved in several external partnerships, including establishing the Structural Genomics Consortium in 2003. Rob joined Heptares Therapeutics in 2011 as Head of Biomolecular Structure, where he is responsible for structural biology and biophysics, computational chemistry and informatics and protein biochemistry, as well as management of external alliances.
Michael Hanson, Ph.D., Director, Structural Biology, Receptos
Michael Hanson's work has been largely focused on pushing the boundaries of structural biology with a focus on crystallography and biophysical characterization of membrane proteins. As such he has been involved in many groundbreaking developments in working with systems such as fatty acid amide hydrolase and more recently G-protein coupled receptors.
In 2002, Michael received his Ph.D. in chemistry from The Scripps Research Institute. After a brief departure from TSRI to join a small startup biotech venture, Michael returned to help lead a program in the Professor Stevens laboratory aimed at developing technology for structurally characterizing the GPCR family of membrane proteins. This effort laid the ground work for three high resolution structures of human G-protein coupled receptors (β2-adrenergic + carazolol (in collaboration with Kobilka lab), β2-adrenergic + timolol and A2A-adenosine receptor) during his tenure at TSRI and many more in the years since his departure in 2009. For his involvement in these efforts, Michael has been an author on numerous papers and received the Sidhu award for advances in x-ray diffraction studies associated with GPCR crystals.
Currently, Michael is leading a structural biology group at Receptos, which was formed in 2009. In his time at Receptos Michael's group has successfully determined several structures of therapeutically important receptor targets, such as the sphingosine 1-phosphate receptor. In addition, his group is actively involved in technology development to enable more robust and rapid structure determination pipelines as well as utilizing purified receptor protein as a tool for direct binding assays and biophysical characterization of protein ligand interactions.
Epigenetic Targets: Chemical Tools
Stephen Edgcomb, Ph.D., Senior Scientist, BPS Bioscience Inc.
Terry Kelly, Ph.D. R&D Manager, Active Motif (formerly from laboratory of Peter Jones)
Elizabeth Quinn, Ph.D., Director, Marketing, LeadHunter, DiscoveRx Corp
This course will focus on what a chemist needs to know regarding epigenetic targets. It will start with a biology review of epigenetic modifications and then address challenges in designing probes and inhibitors for various EPG modifiers. Issues such as optimizing compounds for selectivity, potency and avoidance of toxicity will also be covered.
- Targeting Histone Methyl Transferases (HMTs)
- Inhibiting Demethylases (DMTs)
- Designing Histone Deacetylase Inhibitors (HDACi)
- Bromodomain and extra-terminal (BET) Proteins
Stephen Edgcomb, Ph.D., Senior Scientist, BPS Bioscience Inc.
Dr. Stephen Edgcomb received his Ph.D from the University of Iowa where he investigated the biophysics of protein-protein interactions. During postdoctoral fellowships at the University of California San Francisco and The Scripps Research Institute, he made contributions to the understanding of HIV interactions with human cellular-factors. Stephen joined BPS Biosciences as a Senior Scientist in 2011 where he has developed methods for investigating epigenetic-reader
Terry Kelly, Ph.D. R&D Manager, Active Motif
Terry Kelly received her PhD in Neuroscience from UCLA studying brain and spinal cord neural stem cells. Based on her graduate work she became interested in epigenetics and joined Peter Jones's lab as a post-doctoral fellow studying the roles that epiegentic mechanisms play in the cell cycle, development and cancer. During her post-doctoral work she co-authored many important papers and also developed NOMe-seq, which is an assay that visualizes DNA methylation and nucleosome positioning at base pair resolution from the same DNA strand and subsequently collaborated with Active Motif to modify NOMe-seq for commercialization.
In 2011, she received a prestigious K99R00 Career Development Grant from the NCI which provides 2 years of mentored and 3 years of independent funding to start her own lab. However rather than pursuing a tenured faculty position in 2013, she joined Active Motif as the R&D manager in San Diego where she plans to continue developing epigenetic tools and reagents for the scientific community while also examining the role of epigenetics mechanisms in the nervous system and how they are altered in brain cancer.
Elizabeth Quinn, Ph.D., Director, Marketing Manager, LeadHunter Discovery Services, DiscoveRx Corporation
Elizabeth Quinn received her Ph.D. in Molecular Medicine and Genetics from Wayne State University where her research focused on retroviral transduction of activated T-cells and the development of novel gene therapy strategies for the treatment of hematologic malignancies. She completed a 3 year post-doctoral research fellowship at Stanford University in the area of Hepatitis C pathogenesis. Elizabeth then joined Clontech Laboratories, Inc. as an application scientist and co-developed customized whole genome sequencing and SNP detection kits with several large pharma customers. After 3 years of varied and increasing responsibility within R&D, she moved into Marketing and then joined DiscoveRx as a Senior Product Manager in 2008. During her tenure at DiscoveRx, she successfully launched the consumable cell-based assay product line and next generation GPCR screening and profiling platform that measures receptor internalization. Elizabeth now serves as Marketing Director for the LeadHunter Discovery Services division at DiscoveRx. She is an active member of AACR and has been an invited speaker at major trade
show Tutorial and Workshop sessions and has presented at multiple academic, pharmaceutical and biotech companies within the drug discovery community.