Cambridge Healthtech Institute’s 15^th Annual Mastering Medicinal Chemistry conference will bring together senior level medicinal chemists in pharmaceuticals, biotech, and academia. Through new case studies, informative panel discussions, high-level poster presentations, and interactive breakout discussions, top scientists will share new insights into small molecules. This event will cover key topics currently facing medicinal chemists, including emerging targets, receptor kinetics and high-throughput experimentation. The Mastering Medicinal Chemistry conference- Part 2 will highlight pivotal case studies in a variety of therapeutic areas, including inflammation, respiratory, cardiovascular, metabolic and CNS diseases.

Final Agenda

Wednesday, June 20

11:00 am Registration Open (America Foyer)

11:50 Bridging Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own

12:20 pm Dessert and Coffee Break in the Exhibit Hall with Poster Viewing (America Ballroom)

1:00 PLENARY KEYNOTE SESSION
Essex South

2:30 Refreshment Break in the Exhibit Hall with Poster Viewing (America Ballroom)

APPROACHES TO OPTIMIZATION AND CHARACTERIZATION
Gloucester (2nd Floor)

3:10 Chairperson’s Opening Remarks

Aleksandra Baranczak, PhD, Senior Scientist, Chemistry and Chemical Biology, AbbVie

3:15 Approaches to Cellular Characterization of Small Molecule Protein Binders

Aleksandra Baranczak, PhD, Senior Scientist, Chemistry and Chemical Biology, AbbVie

The field of chemical biology has proven its critical role in enabling the mechanistic characterization of drug candidates in the context of preclinical research. I will discuss the efforts of chemical biology group at AbbVie to determine chemical and proteomic methods for target identification and validation in live cells. The strengths and limitations of all methods will be analyzed, as well as their adaptability to high-throughput format assay development.

3:45 Innovative Technologies Packages for Kinase Drugs with Diverse Inhibition Modes

Lars Neumann, PhD, Associate Director Screening & Technologies, Proteros Biostructures GmbH

4:15 Sponsored Presentation (Opportunity Available)

4:45 Drug Leads Originating from the Public/Private Consortium: European Lead Factory

Dimitrios Tzalis, PhD, CEO Taros Chemicals GmbH & Co. KG

The European Lead Factory is a public-private partnership that provides researchers in Europe a unique platform for translating innovative biology and chemistry into high-quality starting points for drug discovery, 200.000 de novo synthesized compounds are complimenting 300.000 compounds provided by participating pharmaceutical partners. So far resulted in >5.000 hit compounds with a defined biological activity from >90 successfully completed HTS and hit evaluation campaigns out of which a significant number of targets are PPIs.

5:15 Positive Allosteric Modulators for Melanocortin Receptors

Craig W. Lindsley, PhD, Vanderbilt Center for Neuroscience Drug Discovery

Positive allosteric modulators of melanocortin receptors, especially allosteric potentiators of the receptors MC3R and MC4R are described herein. Also provided are pharmaceutical compositions containing the positive allosteric modulators and methods of treating obesity or an obesity-related disorder such as type 2 diabetes, comprising administering an effective amount of the positive allosteric modulator.

5:45 Close of Day and Dinner Short Course Registration*

*Separate registration required.

Thursday, June 21

7:30 am Registration Open (America Foyer) and Morning Coffee (Foyer)

APPROACHES TO OPTIMIZATION AND CHARACTERIZATION (CONT)
Gloucester (2nd Floor)

8:00 Chairperson’s Remarks

Catherine Lebrun, PhD, Medicinal Chemist, Medicinal Chemistry, EMD-SERONO

8:05 3D-Fragments: A Short Path for the Design of Low Mw Cyclophilin D Inhibitors

Catherine Lebrun, PhD, Medicinal Chemist, Medicinal Chemistry, EMD-SERONO

Cyclophilins, or peptidyl-prolyl isomereases (PPAses), play a critical role in multiple cellular pathways. Cyclophilins have been proposed as potential targets for the treatment of a number of diseases such as viral infections, inflammation, neurologic disorders, cardiac failure, and cancer. Until recently, only high molecular weight macrocyclic peptides were described as modulators of this target class. Here we describe a design of potent small molecular weight Cyclophilin D inhibitors starting from weak fragments that bind Cyclophilin D

8:50 Project Tractability: When Enough is Enough

Jeremy Edmunds, PhD, Director, Immunology Medicinal Chemistry, AbbVie

9:35 Find Your Table and Meet Your Moderator

9:40 Interactive Breakout Discussion Groups

This session features various discussion groups that are led by a moderator/s who ensures focused conversations around the key issues listed. Attendees choose to join a specific group and the small, informal setting facilitates sharing of ideas and active networking.

Public-Private Partnerships in Drug Discovery

Dimitrios Tzalis, PhD, CEO Taros Chemicals GmbH & Co. KG

• How can collaborative public-private partnerships foster drug development?
• What steps are being taken to close the “innovation gap”?
• How can partnerships be beneficially for both parties?

Challenges in Phenotypic, Target Agnostic Drug Discovery

Jesus Medina, PhD, Manager, Medicinal Chemistry, GlaxoSmithKline

• Key challenges in cell-based phenotypic drug discovery efforts
• Early assessment of the validity and viability of hits obtained from screens
• What aspects of phenotypic drug discovery are the most advantages in drug discovery

10:20 Coffee Break in the Exhibit Hall with Poster Viewing (America Foyer)

11:05 Drug Target Kinetics and Drug Discovery

Peter Tonge, PhD, Professor, Chemistry, Stony Brook University

Drug selectivity is normally based on equilibrium parameters such as IC50 values. However, since time-dependent target engagement is a function of both the thermodynamics and kinetics of drug-target interactions, drug selectivity also has a kinetic component. Here we discuss the relationship between kinetic selectivity and therapeutic window, the role that factors such as target vulnerability and target turnover play in the translation of kinetic selectivity, and PK/PD models that integrate drug-target kinetics into predictions of drug activity. Several systems will be discussed including inhibitors of Bruton’s tyrosine kinase (Btk).

11:35 Late Breaking Presentation

12:05 pm Discovery of Small Molecule Macrocycles as Powerful Modulators of Cystic Fibrosis and Potent Flaviviral Protease Inhibitors for the Treatment of Zika and Dengue Virus Infections

Helmut Thomas, PhD, DABT, President and CEO, Cyclenium Pharma, Inc.

Cyclenium Pharma has designed a unique small-molecule (CMRT™) macrocycle technology with conventional small-molecule like properties for drug discovery on difficult targets. CMRT compounds are stable chemically and metabolically, demonstrate exceptional safety due to their target specificity as a consequence of their constrained and stereochemically defined nature, and display good cell penetration and oral bioavailability. Initial screens have spawned more than a dozen early programs with protein-protein interactions, enzymes, receptor kinases and brain-bound GPCRs as targets. The discovery of a triple active modulator of cystic fibrosis as a unique example for a protein-protein interaction stabilizing compound as well as a potent pan-inhibitor of flaviviral proteases will be presented as examples of the versatility of this technology.

12:35 Session Break

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

12:35 Networking Luncheon in the Exhibit Hall with Poster Viewing (America Ballroom)

APPROACHES TO LEAD DISCOVERY OPTIMIZATION AND CHARACTERIZATION
Gloucester (2nd Floor)

1:55 Chairperson’s Remarks

Barry Morgan, PhD, Chief Scientific Officer, HitGen Inc.

2:00 Managing Serendipity in Pre-Clinical Small Molecule Drug Discovery: 25 Years of DNA Encoded Chemistry

Barry Morgan, PhD, Chief Scientific Officer, HitGen Inc

Drug discovery and development is a high risk endeavor, and indeed many drugs that profoundly changed the treatment of disease owe their origins in part to good fortune. We will review the economics of early stage drug discovery and consider the impact of DNA encoded libraries, a recent technology that promises to bring a resolution to the budgetary challenges experienced by both industrial and academic centers engaged in small molecule drug discovery.  

2:30 Integration of Chemogenomics Data for Applications in Chemical Biology

Anne Mai Wassermann, PhD, Associate Principal Scientist, Cheminformatics, Merck

3:00 PANEL DISCUSSION:

Moderator: Barry Morgan, PhD, Chief Scientific Officer, HitGen Inc

Panelists: Speakers of the Session

4:00 Close of Conference