Final Agenda June 19-21, 2013 Structure-Based Drug Design · 2013-05-17 · regarding our Structure-Based Drug Design conference. The growing protein structure information has given

Structure-BasedDrug DesignGenome to Drug Lead with Big Data Approach

Cambridge Healthtech Institute and Bio-IT World’s Thirteenth Annual

June 19-21, 2013 • The revere Hotel • Boston, MA

Organized by: Cambridge Healthtech Institute healthtech.com/SBD

Register by May 17 & save up to $200!

Corporate sponsors:

Keynote Presentation:Drugging the Undruggable: Transforming Nature’s α-Helix into Breakthrough Medicines Tomi Sawyer, Ph.D., CSO, Aileron Therapeutics

Final Agenda

Structure-BasedDrug Design

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Dear Colleague,

Thank you for your continued interest and support regarding our Structure-Based Drug Design conference.The growing protein structure information has given structure-based methods a place of prominence in drug discovery. The current state of in silico technology for effectively using biological big data for structure-based drug design is significantly limited by the lack of a realistic environment for simulations and an absence of fully integrated infrastructure. Moreover, the emerging deluge of biological data of all kinds available to the field of biomedicine and the pharmaceutical industry represents a significant opportunity to fundamentally change the process of disease target discovery and drug design. Leveraging ever-increasing computing power and large-scale informatics framework that integrate functional, structural and expression information, we face ample opportunities to fine-tune our protein-ligand modeling algorithm and modify the molecule to get the desired properties.

In silico approaches to rational structure-based drug discovery are leveraging big data technology in the identification and optimization of lead compounds and the identification and validation of drug targets, followed by the prediction of ligands for the target protein from molecular modeling computation.

At CHI’s thirteenth annual Structure-Based Drug Design conference, you will hear about developments in in silico technology, as well as experimental approaches useful for accurately predicting and modeling the structures of proteins in structure-based drug design efforts. In addition, examples of successful applications of such technology approaches to genome-to-drug lead investigations will be addressed.

Register by March 22 at the early rate and save up to $350 off your conference registration.

Warmest regards,

Ming GuoConference DirectorCambridge Healthtech Institute

“Given both the overwhelming amount of available data and the fact that traditional pharma approaches to innovation seem to have largely run out of steam, a bet on big data analytics might make a lot of sense now.”

- David Shaywitz, M.D., Ph.D., Physician, Scientist and Management Consultant

Who You Will Meet

Titles:• Lab Head/Head

• Team Leader

• Chief Scientific Officer

• Director

• Research Scientist/Principal Scientist/Scientist

• Senior Researcher/Researcher

• Graduate Student

• Professor

• PostDoc

Departments:• Biochemistry

• Bioinformatics

• Chemical Biology

• Chemistry

• Computational Biology

• Computational Chemistry

• Discovery Chemistry

• Drug Discovery

• Informatics

• Lead Discovery

• Medicinal Chemistry

• Molecular Modeling

• Scientific Computing

• Stuctural Biology

• Structural Chemistry

• Structural Sciences

Co-Located Event:Eleventh Annual

Next-Gen Kinase Inhibitors:Moving Towards a Successful Pipeline

June 17-19

healthtech.com/KIN

BESt VALuE! Register for the Structure-Based Drug Design and Kinase conferences at a special rate.

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WEDNESDAY, JUNE 19

MoRning ShoRT CouRSe (JUNe 19, 9:00 AM-12:00 PM)* Structure-Based Drug Design for epigenetic TargetsJohnathan R. Whetstine, Ph.D., Assistant Professor of Medicine, Harvard Medical SchoolPhilip Fallon, Ph.D., Senior Medicinal Chemist, Domainex Ltd.

*Separate registration required.

STRUCTURE-BASED DRUG DESIGN FOR KINASE

1:15 pm Chairperson’s opening RemarksAdam C. Palmer, Ph.D., Postdoctoral Fellow, Department of Systems Biology, Harvard Medical School

1. the special role that structure-based drug design can play in treating drug resistant infectious diseases

2. how considering the evolution of resistance during drug development could produce drugs with more long-lasting clinical efficacy

3. how drug resistance can be used as a tool to understand mechanism of drug action

1:20 Structure-Based Design of Potent and Selective inhibitors of Pi3-Kinase DeltaJeremy M. Murray, Ph.D., Scientist, Structural Biology, GenentechInhibition of PI3Kδ is considered to be an attractive mechanism for the treatment of inflammatory diseases and leukocyte malignancies. Using a structure-based design approach, we have identified a series of potent and selective inhibitors of PI3Kδ. These inhibitors do not occupy the induced selectivity pocket between Trp760 and Met752 that is observed for other families of selective PI3Kδ inhibitors. Instead, the selectivity of the compounds for inhibition of PI3Kδ relative to other PI3K isoforms appears to be due primarily to the strong interactions these inhibitors are able to make with Trp760 in the PI3Kδ binding pocket. This talk will discuss the structural understanding of the selectivity of these inhibitors against other isoforms, pharmacokinetic properties and the ability of select compounds to inhibit the function of B-cells in vivo.

1:50 MD Simulations of Mutant and WT Pi3Kα: insights into the Mechanism of overactivation and implications for Drug DesignZoe Cournia, Ph.D., Investigator, Biomedical Research Foundation, Academy of AthensPI 3 kinase alpha (PI3Kα) is one of the most frequently mutated proteins in human cancers. Molecular dynamics simulations in aqueous solution performed for wild type (WT) and H1047R mutant PI3Kα proteins, revealed different dynamical and structural features for the two proteins, which may lead to kinase overactivation in the mutant variant. Binding site prediction and virtual screening further facilitated the development of novel mutant-specific PI3Kα inhibitors that exploit the altered conformation of the mutant with respect to the WT protein.

DRUG RESISTANCE

2:20 guiding the Design of Robust inhibitors Targeting hiV and hCV Proteases by using the Dynamic Substrate envelopeAysegul Ozen, Ph.D. Candidate, Biochemistry & Molecular Pharmacology, University of Massachusetts Medical SchoolDrug resistance is a major concern in the treatment of quickly evolving diseases. At the molecular level, drug resistance reflects a subtle change in the balance of molecular recognition by the target enzyme due to mutations in favor of substrate processing versus inhibitor binding. Robust inhibitors can be designed by mimicking the binding features of the natural substrates to minimize the chances of resistance.

2:50 Refreshment Break in the exhibit hall with Poster Viewing

3:30 Towards a new generation of Animicrobial AntifolatesDennis L. Wright, Ph.D., Professor of Pharmaceutical Sciences and Chemistry, University of ConnecticutWe are using a structure-based design approach to develop potent and selective inhibitors of the enzyme dihydrofolate reductase (DHFR) from a variety of pathogenic organisms. Analysis of crystal structures

of trimethoprim-resistant and naturally-insensitive enzymes led to the design of a series of propargyl-linked antifolates characterized by high potency, good selectivity over the human form of the enzyme and good anti-microbial activity.

4:00 understanding Drug Mechanism of Action by Target gene overexpressionAdam C. Palmer, Ph.D., Postdoctoral Fellow, Department of Systems Biology, Harvard Medical SchoolThe molecular targets of drugs can sometimes, but not always, be identified amongst genes that confer drug resistance when overexpressed. We quantitatively overexpressed genes encoding

known antibiotic targets and observed that drug resistance does not only increase; it can remain unchanged, decrease, or even have a non-monotonic dependence on target expression. These diverse effects are explained by simple models considering gene toxicity and drug-induction of harmful target-catalyzed reactions. The relation between drug resistance and target expression may reveal unexpectedly complex mechanisms of drug action.

4:30 Close of the Day

DinneR ShoRT CouRSe (JUNe 19, 6:00-8:00 PM)*A uniform Framework for Computer-Aided Biologics DesignChris Williams, Ph.D., Principal Scientist, Chemical Computing Group

*Separate registration required.

Sponsored by

THURSDAY, JUNE 20

7:30 am Morning Coffee

8:30 Chairperson’s RemarksEdward R. Zartler, President and CSO, Quantum Tessera Consulting, LLC

» KEYNOtE PRESENtAtION:8:40 Drugging the undruggable: Transforming nature’s α-helix into

Breakthrough MedicinesTomi Sawyer, Ph.D., CSO, Aileron TherapeuticsA major challenge of drug discovery has been to successfully modulate the biological properties of those therapeutic targets deemed “undruggable” as defined relative to small-molecules.

However, recent advancements leveraging peptides and macrocycles are expanding such drug space, especially for many intracellular protein–protein interaction targets deemed “hot” drug-wise. Structural biology and computational chemistry are key tools for such drug discovery. As a case study, advancements in stapled peptide technology to transform Nature’s α-helix into breakthrough medicines will be presented.

9:10 A Beacon in the Dark: Structural information in the Absence of StructureEdward R. Zartler, President and CSO, Quantum Tessera Consulting, LLCThe current (and next) generation of drug targets are very difficult to ligand: membrane proteins, multimeric protein complexes, post-translationally modified proteins, protein-protein interactions. Advances in structural biology have been made where we can obtain

high resolution structural information for many of these targets. However, for a large swath of the current, and next-gen targets, we are simply working in the structural dark. Recent advances in NMR-based methods, coupled with novel ideas in fragment-based hit generation, can now shine a light into this darkness, yielding crucial structural details to allow ligands to be rationally designed. We will discuss these advances and their application to drug discovery.

FORCE FIELD CALCULATION

9:40 Docking: is it Possible to Know When it Works?Sponsored by

Greg Warren, Ph.D., Senior Applications Scientist, OpenEye Scientific Software, Inc.It is commonly held that the same, protein-centric approach, can be used successfully both to predict the bound conformation of a ligand in complex with a given protein (pose prediction) and to rank molecules based on their probability of being a binder to that protein (structure-based virtual screening). We will present tools in the OEDocking Suite that approach these two problems as issues of a rather different nature. Successful results in virtual screening using the rigid protein approximation in docking will be presented along with a flexible, ligand-centric approach to pose prediction that is much more reliable than traditional protein-centric posing tools. We also show that whether the problem is pose prediction or virtual screening, combining ligand and protein information in the same calculation

Structure-BasedDrug Design

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produces better results.

10:10 Coffee Break in the exhibit hall with Poster Viewing

10:40 incorporating Ligand Polarisation in Binding Free energy CalculationsJonathan W. Essex, Ph.D., Professor, Head, Computational Systems Chemistry, Chairman, Institute for Complex Systems Simulation (ICSS), School of Chemistry, University of SouthamptonWhile the methods underpinning the calculation of protein-ligand binding free energies are well understood, accurate calculations are

still fundamentally limited by inadequate sampling of the protein-ligand complex, and inaccurate modeling of the associated intermolecular interactions. To address the second issue, we have developed a simple and computationally inexpensive correction to the calculated free energies based on a hybrid quantum mechanics/molecular mechanics approach. In this presentation, the method will be described and its performance assessed in the calculation of small and drug-like molecules’ free energies of hydration, and on the calculation of protein-ligand binding affinities in neuraminidase, CDK2 and COX2.

11:10 Site identification by Ligand Competitive Saturation (SiLCS): Structure-Based Free energy Computational Approach for Ligand Discovery and optimizationAlexander D. MacKerell, Jr., Ph.D., Grollman-Glick Professor of Pharmaceutical Sciences, Director, Computer-Aided Drug Design Center,

School of Pharmacy, University of MarylandThe Site Identification by Ligand Competitive Saturation (SILCS) method uses explicit solvent all-atom molecular dynamics simulations to identify binding sites on proteins for functional group classes based on rigorous free energy criteria that includes protein flexibility and fragment desolvation. Information from the SILCS approach, termed FragMaps, may be used for the identification of novel ligands targeting protein, including de novo ligand design. In addition, the SILCS method may be combined with structural information on a ligand-protein complex to facilitate modification of the ligand to improve its binding affinity.

11:40 Blurring to Bring Binding Free energies into FocusKenneth M. Merz, Jr., University of Florida Research Foundation Professor, Edmund H. Prominski Professor of Chemistry, Department of Chemistry, Quantum Theory Project, University of FloridaDocking calculations coupled with binding free energy estimates (scoring) are a mainstay of structure-based drug design. This talk

addresses how to use ensemble principles to estimate and reduce uncertainty of computed binding free energies. We have developed methods to evaluate potential function error and in this talk we will demonstrate how to use this knowledge to improve the outcome of a docking and scoring exercise. This was accomplished via the development of novel scoring approaches that employ statistical mechanical principles and are coupled with error propagation. Importantly, our approach yields free energies as well as estimates of the random and systematic errors in these quantities, providing insight into the reliability of the computed free energies.

12:10 pm enjoy Lunch on Your own

GPCR

1:30 Chairperson’s RemarksZoe Cournia, Ph.D., Investigator, Biomedical Research Foundation, Academy of Athens

1:40 An Automated Pipeline for the Modeling and Simulation of gPCRs: Applications to Structure-Based Drug DesignHugo Gutierrez de Teran, Ph.D., Department of Cell and Molecular Biology, Uppsala UniversityThe recent advances in membrane protein crystallography have provided extremely valuable structural information of the superfamily

of G-protein-coupled receptors (GPCRs). Recently, we have developed GPCR-ModSim (http://gpcr.usc.es), a web-based, automated pipeline to generate high-quality 3D models of the remaining GPCRs and to perform molecular dynamics (MD) simulations with an explicit representation of the cellular membrane, structural water, cholesterol or lipid molecules. With this computational tool, research groups without prior experience in computational chemistry can set up ambitious projects on SBDD in GPCRs in a systematic and comprehensive way.

2:10 how Drugs Bind and Control Their Targets: Characterizing gPCR Signaling through Long-Timescale SimulationRon O. Dror, Senior Research Scientist, D. E. Shaw Research One-third of drugs act by binding to G protein–coupled receptors (GPCRs) and either triggering or preventing receptor activation, but the process by which they do so has proven difficult to characterize either

experimentally or computationally. Anton, a special-purpose machine that we designed to accelerate molecular dynamics simulations by orders of magnitude, has enabled simulations in which drugs spontaneously associate with GPCRs to achieve bound conformations that match crystal structures almost perfectly. Anton simulations have also captured transitions of a GPCR between its active and inactive states, allowing us to characterize the mechanism of receptor activation. Our results suggest opportunities for the design of drugs that achieve greater specificity and control receptor signaling more precisely.

WATER & SOLVATION IN DRUG DESIGN

2:40 exploiting Solvent effects in Drug Design and optimization Sponsored by

Chris Williams, Ph.D., Principal Scientist, Chemical Computing GroupUpon ligand binding, solvent molecules around the binding pocket and the ligand become displaced or rearranged. These desolvation energies can be a significant portion of the total binding energy, and thus represent opportunities for ligand design. Computing desolvation energetics typically requires lengthy simulations, but this talk presents a fast and easy-to-use method (3D-RISM) which computes desolvation energies in minutes, without using explicit simulations. Application to ligand optimization is demonstrated using case studies.

3:10 Refreshment Break in the exhibit hall with Poster Viewing

3:40 Characterizing and exploiting the Solvation of Protein Surfaces for Applications in Drug Design and DiscoveryTom Kurtzman Young, Ph.D., Assistant Professor, Department of Chemistry, Lehman College, CUNYThe displacement of water from a binding site by a ligand is a principal, and often dominant, source of binding free energy. In recent years, a number of techniques based on Inhomogeneous Solvation Theory have been developed that map out the solvation thermodynamics of protein binding sites (STOW, WaterMap, GIST). We outline the physical basis of these mapping techniques and present some possible applications in drug discovery and design.

4:10 Mapping Protein Surfaces with MixMD to identify new Binding SitesHeather Carlson, Professor, Medicinal Chemistry, University of MichiganMixed-solvent molecular dynamics (MixMD) is an emerging technique in structure-based drug design (SBDD). The most significant benefits are the ability of a protein to adapt in the presence of a probe and the identification of binding sites where organic molecules specifically out-compete water.

Rather than ignoring the complicated role of water as most SBDD methods do, it is truly embraced in MixMD. Blinded, experimental validation of the method will be presented.

4:40 The Potency-insolubility Conundrum in Drug Discovery: Mechanism and Solution for hepatitis C inhibitorsPatrick R. Connelly, Ph.D., Principal Scientific Fellow, Vertex Pharmaceuticals, Inc.As compounds are optimized for greater potency during pharmaceutical discovery, their aqueous solubility often decreases,

making them less viable as orally-administered drugs. The potency-insolubility conundrum has prompted speculation, concern, and attempts to taxonomize the problem or overcome it technologically. However, a fundamental molecular connection between binding potency and aqueous insolubility has yet to be elucidated. By examination of the structural and thermodynamic properties of telaprevir, a sparingly soluble inhibitor of the NS3 protease of the Hepatitis C virus, it is revealed that potency and insolubility share a common origin. A design strategy based on supramolecular graph set considerations provides a generalizable solution to the conundrum.

5:10 Welcome Reception in the exhibit hall with Poster Viewing

6:30 end of Day

FRIDAY, JUNE 21

7:30 am Breakfast Roundtable Discussions

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Table 1. Discovering Allosteric Binding Pockets

• Motivation• Discuss existing methodologies• Exchange ideas, Propose future schemes

Moderator: Zoe Cournia, Ph.D., Investigator, Biomedical Research Foundation, Academy of Athens

Table 2. The Role of Structure-Based Approaches in understanding Polypharmacology

• The many roles of structure-based approaches on polypharmacology• How can we effectively compare binding sites?• How can we optimize the use of fragment-based approaches to modulate the

binding to several targets?• Are free-energy methods ready to deal with selectivity issues?

Moderator: Hugo Gutierrez de Teran, Ph.D., Guest Researcher, Cell and Molecular Biology, Uppsala University

Table 3: Drug Resistance

• The special role that structure-based drug design can play in treating drug resistant infectious diseases

• How considering the evolution of resistance during drug development could produce drugs with more long-lasting clinical efficacy

• How drug resistance can be used as a tool to understand mechanism of drug action

Moderator: Adam C. Palmer, Ph.D., Postdoctoral Fellow, Department of Systems Biology, Harvard Medical School

FRAGMENT-BASED DRUG DESIGN

8:30 Chairperson’s RemarksWoody Sherman, Ph.D., Vice President, Applications Science, Schrodinger, Inc.

8:40 Case histories of Recent Fragment-Based Drug Discovery ProjectsChristopher W. Murray, Ph.D., Vice President, Discovery Technology, Astex PharmaceuticalsHere we describe some case histories of applying fragment-based drug discovery to challenging drug targets. This will include the design of protein-protein interaction inhibitors of IAP family proteins and the

design of allosteric inhibitors of full-length NS3 proteins from the Hepatitis C Virus. The presentation will discuss the difficulties associated with applying fragment-based drug discovery to challenging target classes and will discuss ways in which these can be mitigated.

9:10 Computational Protein Mapping to Drive the Development of Fragment hits into LeadsSandor Vajda, Ph.D., Professor of Biomedical Engineering and Chemistry, Director, Biomolecular Engineering Research Center, Boston UniversityFragment-based drug design (FBDD) starts with finding fragment-sized compounds that are highly ligand efficient and can serve as a core moiety for developing high-affinity leads. Although the core-bound structure of a protein facilitates the construction of leads, effective design is far from straightforward. We show that

protein mapping, a computational method developed to find binding hot spots, provides information that complements the fragment screening results and can drive the evolution of core fragments into larger leads with a minimal loss or, in some cases, even a gain in ligand efficiency.

9:40 Determination of Binding Poses, Kinetics and energetics in Fragment-Based DesignGianni De Fabritiis, Ph.D., Computational Biophysics Laboratory (GRIB-IMIM), Universitat Pompeu Fabra, Barcelona Biomedical Research Park (PRBB)

Recently, we have been able to quantitatively reconstruct the complete binding process of several molecular systems in terms of binding poses, kinetics, affinities and pathways of binding. The key to reaching the timescales (microseconds and beyond) of these processes is high-throughput molecular dynamics, i.e. the capability to generate and then analyze thousands of MD short trajectories. I will discuss the technology involved to reach these timescales and highlight the novel insights we have obtained regarding protein-ligand complexation.

10:10 Coffee Break in the exhibit hall with Poster Viewing

10:40 The Tip of the iceberg and the Chemical universe: Fuzzy hit Finding under Synthetic Feasibility ConditionsCarsten Detering, Ph.D., CEO, BioSolveIT, Inc.We have come up with a method that addresses the problem of crowded patent space. It captures existing available chemistry in a company and thus allows the researcher to fuzzily search in a larger

portion of the chemical universe available to him/her. Results are returned with their underlying chemical synthesis, which renders retro-synthesis unnecessary. Time saved can be invested in other Medicinal Chemistry efforts. The talk will highlight the method as well as several application examples.

11:10 Advances in Predicting Protein-Protein Binding Affinity and Protein Stability

Sponsored by

Woody Sherman, Ph.D., Vice President, Applications Science, Schrodinger, Inc.The field of biologics continues to grow in importance in the pharmaceutical industry. To address the increasing need for

computational tools to model biologics we have developed the Biologics Suite, which contains a broad range of task-driven applications tailored specifically to the field of biologics. Our objective was to blend an easy-to-use interface with state-of-the-art molecular simulations and de novo prediction, providing researchers with access to intuitive modules for protein-protein docking, estimation of residue mutation effects, disulfide stabilization, antibody modeling, determination of aggregation hotspots, and additional advanced simulations. Here, we present validation work on a sampling of the modules.

11:40 Q&A with Morning Speakers

12:00 enjoy Lunch on Your own

PROTEIN-PROTEIN INTERACTION

1:25 Chairperson’s RemarksDafydd Owen, Ph.D., Associate Research Fellow, Biotherapeutics Worldwide R&D, Pfizer Worldwide Medicinal Chemistry

sponsoring society:

Media sponsor:

Media partners:

healthtech.com/SBD ••• 6

1:30 how Does a Small-Molecule inhibitor Bind at the Protein-Protein interface of interleukin 2?Yibing Shan, Senior Scientist, DE Shaw ResearchAn increasingly important new frontier of drug discovery centered on using small-molecule inhibitors to selectively bind at the interfaces of specific protein-protein interactions (PPI) involved in disease

development.  A great challenge in the design of PPI inhibitors, however, lies with the fact that the geometrical features of PPI binding sites are often invisible prior to the binding.  Thus understanding how a small molecule binds and how the binding site arrives at the bound conformations in this process is highly desirable.  To this end, we conducted unguided molecular dynamics to simulate the complete molecular process of a small molecule SP4206 binding to interleukine-2α (IL-2α) protein.  In two of these simulations, the small molecule correctly identified its target binding site, forming a complex virtually identical to the crystallographically determined bound structure.  The simulations provided an atomic-level view of the process by which a small molecule binds at the relatively flat protein-protein interface while the binding site adopts its bound conformation. These simulations indicated that the binding process of SP4206 is one of induced fit.  Similarly simulations of IL-2α interactions with chemical fragments including fragments of SP4206 further suggested that specific interaction of a chemical fragment and a protein requires a threshold molecular weight for the fragment

2:00 From Determinants of RunX1/eTo Tetramerization to Small-Molecule Protein-Protein interaction inhibitors Targeting Acute Myeloid LeukemiaHolger Gohlke, Ph. D., Professor, Institute of Pharmaceutical and Medicinal Chemistry, Heinrich-Heine-University, Düsseldorf

A promising way to interfere with biological processes is through the control of protein-protein interactions by means of small molecules. Recent advances in the understanding of the energetics and dynamics of protein-binding interfaces open up a way to apply rational design approaches for finding protein-protein interaction modulators (PPIM). Here, we successfully identify small-molecule inhibitors of the dimer to tetramer transition of the NHR2 domain within the RUNX1/ETO fusion protein, a novel target for the treatment of acute myeloid leukemia.

2:30 Structure-Based guided Development of Focused Chemical Library Dedicated to orthosteric Modulation of Protein-Protein interactions

Xavier Morelli, Ph.D., Group Leader, Cancer Research Center of Marseille, CNRSThis talk will address some challenging issues: biological and chemical spaces of PPI with known orthosteric inhibitors, ligandability assessment of protein-protein interactions, design and validation of

chemical libraries dedicated to PPIs.

3:00 Refreshment Break

EPIGENETIC TARGETING

3:15 Design and Develop Bromodomain inhibitor for Cancer TherapyJun Qi, Ph.D., Senior Research Scientist, Medical Oncology, Dana-Farber Cancer InstituteIn cancer, epigenetic proteins are promising and intensely studied targets for therapeutic drug discovery. Among the chromatin-modifying enzymes, so-called epigenetic “writers”, “readers” and

“erasers”, chromatin-binding modules or epigenetic “readers” have received comparatively little attention perhaps owing to perceptions regarding the difficulty of targeting protein-protein interactions. Motivated by this challenge, we have developed first-in-class, drug-like inhibitors of “bromodomain and extraterminal domain” epigenetic readers (BETs) for mechanistic study and therapeutic application in cancer. We are continuously integrating the transcriptional consequences of BETi with changes in the epigenomic landscapes of cancer cells to elucidate the mechanisms underlying response to BETi using chemical and genetic perturbations.

3:45 The impact of Structural Data on epigenetic Probe Discovery for the Public Domain

Dafydd Owen, Ph.D., Associate Research Fellow, Biotherapeutics Worldwide R&D, Pfizer Worldwide Medicinal ChemistryResearch into the role of epigenetics in disease could be significantly accelerated if cell-active chemical probes for such targets were available to the research community, through a collaborative, open-

innovation model. Pfizer is a member of a public-private partnership led by the Structural Genomics Consortium (SGC) to help identify a suite of high-quality chemical probes for epigenetic targets. This partnership is unique in that it brings the medicinal chemistry expertise within industry together with biological expertise in academia to drive basic research in an emerging area of important biology of potential relevance to many diseases. The impact of structural biology on probe discovery will be presented.

4:15 Closing Remarks

4:30 end of Conference

Structure-BasedDrug Design

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Sponsorship & Exhibit inforMATion

Agenda PresentationsShowcase your solutions to a guaranteed, highly-targeted audience. Package includes a 15- or 30-minute podium presentation within the scientific agenda, exhibit space, on-site branding and access to cooperative marketing efforts by CHI.

Breakfast & Luncheon PresentationsOpportunities include a 30-minute podium presentation. Boxed lunches are delivered into the main session room, which guarantees audience attendance and participation. A limited number of presentations are available for sponsorship and they will sell out quickly. Sign on to secure your talk!

Invitation-Only VIP Dinner/Hospitality SuiteSponsors will hand-pick their top prospects from the conference pre-registration list for an evening of networking at the hotel or at a choice local venue. CHI will extend invitations and deliver prospects. evening will be customized according to sponsor’s objectives (i.e. purely social, focus group, reception style, or plated dinner with specific conversation focus).

Focus GroupsCHI can help you organize and execute a focus group on site. This exclusive gathering can be useful to conduct market research, gain feedback on a new product idea, and gather marketing intelligence from industry experts on a specific topic. Please inquire for more details.

User Group MeetingCo-locate your user group with the Structure-Based Drug Design conference. CHI will help market the event, manage logistical operations, develop an agenda, and more. CHI can handle the entirety of the meeting, or aspects of your choice.

Exhibit Informationexhibitors will enjoy facilitated networking opportunities with qualified decision-makers at the Structure-Based Drug Design conference, making it the perfect platform to launch a new product, collect feedback and generate new leads. exhibit space sells out quickly, so reserve yours today!

Additional Promotional Opportunities Include: • Conference tote bags• Badge lanyards • Tote bag inserts of company literature • Padfolios • Keynote chair drop of company literature • Session room chair drop of company literature • Program guide sponsor

• Poster abstract book sponsor

CHI offers comprehensive sponsorship packages which include presentation opportunities, exhibit space and branding, as well as the use of the pre- and post-show delegate list. Sponsorship allows you to achieve your objectives before, during, and long after the event. Any sponsorship can be customized to meet your company’s needs and budget. Signing on earlier will allow you to maximize exposure to hard-to-reach decision makers.

Looking for additional ways to drive leads to your sales team?CHI can help with custom lead generation programs!

We offer clients numerous options for custom lead generation programs to address their marketing and sales needs. Some of our programs include: live webinars, white papers, market surveys, podcasts, and more!

Benefits of working with CHI for your lead generation needs:

• Your campaign will receive targeted promotion to CHI’s unparalleled database of over 800,000 individuals, all of which are involved in all sectors of the life sciences – lists can be segmented based on geography, research area, title and industry

• All custom lead generation programs are promoted through our experienced marketing team that will develop and drive targeted campaigns to expand awareness and bolster leads

• For our webinar programs, we offer assistance in procuring speakers for your web symposia through our extensive roster of industry recognized speakers across multiple disciplines within life sciences, as well as provide an experienced moderator and dedicated operations team to coordinate all efforts

• If choosing a white paper program, we can offer editorial experience and provide an industry-recognized author to write your white paper

For additional sponsorship & exhibit information, please contact:

Jon StroupManager, Business Development781-972-5483 [email protected]

healthtech.com/SBD ••• 8

Hotel & travel inforMATion

Conference Venue and Hotel:

The Revere Hotel200 Stuart Street, Boston, MA 02116Tel: (617) 482-1800

Discounted Room Rate: $249 s/dDiscounted Reservation Cut-off Date: May 17, 2013

Please visit our website to make your reservations online, or call the hotel directly to reserve your sleeping accommodations. You will need to identify yourself as a Cambridge Healthtech Institute conference attendee to receive the discounted room rate with the host hotel. Reservations made after the cut-off date or after the group room block has been filled (whichever comes first) will be accepted on a space-and-rate-availability basis. Rooms are limited, so please book early.

Flight Discounts:

Special discounts have been established with American Airlines. Please use one of the following methods:

• Call American Airlines at 1-800-433-1790 and use Conference code 4463BU

• Go to www.aa.com/group and enter 4463BU in the promotion discount box

• Contact our dedicated travel agent, Rona Meizler at 1-617-559-3735 or [email protected]

Car Rental Discounts:

Special rental discounts have been established with Hertz for this conference.

• Go to www.hertz.com and use our Hertz Convention number (CV): 04KL0003

• Call Hertz at 1-800-654-3131 and use our Hertz Convention Number (CV):04KL0003

Past Attendee testimonials:“The selection of speakers and presentations strongly demonstrated the expansive breadth and impact of structure-based drug design.”- Director of Bioinformatics, ActivX Biosciences

“Very, very interesting and useful.”- Team Leader, Molecular Modelling, CNRS-ICSN

“Good-quality up-to-date presentations made this a stimulating and informative conference.” - CSO, De Novo Pharmaceuticals Ltd.

“Some discussions inspired new ideas I am going to try.”- Senior Research Fellow, Merck

“Thanks to the organizers, it’s a very exciting conference. It’s very interesting to listen to all the talks. Some discussions inspired new ideas that I’m going to try!” - Senior Research Fellow, Molsys, Merck

“Some important principles were highlighted with regard to the computational problem of describing ligand binding and the computational problem of describing ligand binding and drug-likeliness; and the best thing was that the speakers could demonstrate that working solutions are beginning to emerge.”- Computational Chemist, Bayer HealthCare

“Some very important principles were highlighted and the best thing was that the speakers could demonstrate working solutions.”- Computational Chemist, Bayer HealthCare

“It was great – best conference I’ve been to.”- Scientist, Prothana, Inc.

“A useful meeting where I gained more insights and ideas to apply in my own research.”- Chemistry Specialist, Catholic University Leuven

How to Register: healthtech.com/[email protected] • P: 781.972.5400 or Toll-free in the U.S. 888.999.6288

Please use keycode SBD F

when registering!

ADDItIonAl regIStrAtIon DetAIlSEach registration includes all conference sessions, posters and exhibits, food functions, and access to the conference proceedings link.Handicapped Equal Access: In accordance with the ADA, Cambridge Healthtech Institute is pleased to arrange special accommodations for attendees with special needs. All requests for such assistance must be submitted in writing to CHI at least 30 days prior to the start of the meeting.to view our Substitutions/Cancellations Policy, go to http://www.healthtech.com/regdetailsVideo and or audio recording of any kind is prohibited onsite at all CHI events.

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A series of diverse reports designed to keep life science professionals informed of the salient trends in pharmaceutical technology, business, clinical development, and therapeutic disease markets.For a detailed list of reports, visit InsightPharmaReports.com, or contact Rose LaRaia, [email protected], +1-781-972-5444.

Barnett is a recognized leader in clinical education, training, and reference guides for life science professionals involved in the drug development process. For more information, visit barnettinternational.com.

Cambridge Healthtech Associates™ (CHA™) uses its collaborative model to improve the speed and economics of life sciences R&D, leveraging its consulting, technology evaluations and communities. Visit www.chacorporate.com.

Pricing and registration InformationSHort CoUrSeS

Academic, government, June 19 Commercial Hospital-affiliated

Morning Course: Structure-Based Drug Design for Epigenetic Targets $495 $295Dinner Couse: A Uniform Framework for Computer-Aided Biologics Design $495 $295

ConFerenCe PrICIng

(excludes short course)

Advance Registration until May 17, 2013 $1895 $775Registrations after May 17, 2013, and on-site $2095 $845

SPeCIAl PACkAge PrICIng

(Includes access to Structure-Based Drug Design & next-gen kinase Inhibitors, excludes short course)

Advance Registration until May 17, 2013 $3145 $1415Registrations after May 17, 2013, and on-site $3345 $1435

ConFerenCe DISCoUntS

Poster Submission-Discount ($50 Off)Poster abstracts are due by May 10, 2013. Once your registration has been fully processed, we will send an email containing a unique link allowing you to submit your poster abstract. If you do not receive your link within 5 business days, please contact [email protected]. *CHI reserves the right to publish your poster title and abstract in various marketing materials and products.International Society for Computational Biology (ISCB) Member- Discount 10% Off Subject to verification.

regISter 3 - 4th IS Free: Individuals must register for the same conference or conference combination and submit completed registration form together for discount to apply.

Additional discounts are available for multiple attendees from the same organization. For more information on group rates, contact David Cunningham at +1-781-972-5472.

If you are unable to attend but would like to purchase the Structure-Based Drug Design CD for $350 (plus shipping), please visit www.healthtech.com/sbd.Massachusetts delivery will include sales tax.

CO-LOCATED EVENT

Next-Gen Kinase InhibitorsMoving Towards a Successful Pipeline

June 17-19healthtech.com/KIN

Eleventh Annual BEST VALUE! Register for both conferences at a

special rate.

Structure-BasedDrug DesignCambridge Healthtech Institute and Bio-IT World’s Thirteenth Annual June 19-21, 2013

The revere Hotel Boston, MA