Breakout Discussions - Drug Discovery Chemistry

2020 Archived Content

BREAKOUT DISCUSSIONS

In these group discussions, attendees choose a specific Zoom Room to join. Each group has a moderator to ensure focused conversations around key issues within the topic. The group format allows participants to informally meet potential collaborators, share examples from their work and discuss ideas with peers. You will have the ability to turn on and off your camera and microphone and the session will not be recorded and NOT available On Demand.

TUESDAY, AUGUST 25, 3:45 PM EASTERN DAYLIGHT TIME ZONE

Ubiquitin-Induced Targeted Protein Degradation

Topic: New Technologies and Assays to Target the Ubiquitin-Proteasome System

Moderator: Alexander Statsyuk, PhD, Assistant Professor, Department of Pharmacological and Pharmaceutical Sciences, University of Houston

Key ubiquitination steps for inducing protein degradation
Biochemical, biophysical and cellular-based approaches to monitor ternary complex formation
How to identify novel E3 ligases and E3 ligase ligands: need and challenges
How do PROTACs and IMIDs affect the normal UPS function?

Topic: PROTAC-Based Protein Degradation: Novel Applications and Approaches

Moderator: Tauseef R. Butt PhD, President and CEO, Progenra, Inc.

Current limitations of PROTAC approaches – application of cereblon, cIAP, VHL, HDM2 ligases as degrader molecules ligase
Big hurdles in therapeutic potential of PROTACs – toxicity for chronic diseases; oral bioavailability; IP issues
Expanding therapeutic potential of PROTACs – developing novel ligases for membrane, cytosol or nuclear targets
How to overcome the above hurdles and not develop “Me Too” PROTACs

Fragment-Based Drug Discovery

Topic: Orthogonal Biophysical Techniques for FBDD

Moderator: Charles Wartchow, PhD, Senior Investigator, Novartis Institutes for Biomedical Research

When to use what: SHG, SPR, NMR, DSF
Combining techniques: reconciling data
The importance of biochemical assays in biophysical screening campaigns
Applications to finding allosteric inhibitors

Topic: Covalent Fragments

Moderator: Daniel Erlanson, PhD, Vice President, Chemistry, Frontier Medicines

Reversible vs. irreversible covalent fragments
How to characterize covalent fragments
Chemistries for cysteine and beyond

Kinase Inhibitor Chemistry

Topic: The Future of Kinase Inhibitors

Moderator: Hatylas Azevedo, PhD, MBA, R&D Manager, Drug Discovery, Aché Laboratórios

Allosteric inhibitors
Artificial intelligence
Different scaffolds (natural products, macrocycles, covalent inhibitors)

Macrocyclics & Constrained Peptides

Topic: Lead ID Using Macrocycle Libraries

Moderator: Adrian Whitty, PhD, Associate Professor of Chemistry, Boston University

What properties define a good macrocycle screening hit?
What represents good potency, and does this depend on library chemistry?
Specialized/biased versus general purpose libraries

Topic: Technologies Driving Macrocycle Innovation

Moderator: Cameron Pye, PhD, CEO & Co-Founder, Unnatural Products

Hit-finding strategies: DELs, mRNA display, phage, next-gen OBOC, biosynthesis. Where do they work, where do they struggle?
Early prioritization: modeling or empirical property-based selection?
What is missing? What technologies could rapidly enhance macrocycle discovery and development? Better modeling, more efficient synthesis, more diverse hits...?

THURSDAY, AUGUST 27, 11:00 AM EASTERN DAYLIGHT TIME ZONE

Protein-Protein Interactions

Topic: Biophysical Hit Assessment for PPI Targets

Moderator: Mary Harner, PhD, Research Investigator II, Mechanistic Biochemistry, Bristol-Myers Squibb R&D

Molecular properties: eliminating false positive hits
Target engagement technology selection 101: TSA, NMR, MST, SPR, other
Improving confidence by combining technologies
Importance of controls: reference molecules, specificity targets
Delineating hits: mechanism of binding, binding site elucidation

Topic: Applications of 19F NMR for Ligand Discovery

William CK Pomerantz, PhD, Associate Professor, Medicinal Chemistry, University of Minnesota Twin Cities

What types of 19F NMR experiment should I choose for a given target. E.g. Direct binding ligand-observed vs protein-observed, or competition based ligand observed
What are the practical and technical limitations from the various methods available for fragment screening
What drug targets are well-suited for 19F NMR screening

Artificial Intelligence for Early Drug Discovery

Topic: AI-Driven Target Discovery and Therapies

Moderator: Ruben Abagyan, PhD, Professor, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego

Types of AI models predicting individual target activities of small molecules
May the docking be a useful intermediate step before the AI model is applied?
How under-characterized is the set of activities of small molecule therapeutics and drug candidates?

Topic: Trends in AI for Accelerating Drug Discovery

Moderator: Amol Jadhav, PhD, Industry Consultant, Transformational Health, Frost & Sullivan

Current trends for the application of AI towards preclinical drug discovery, status and challenges
What measures should be taken to invest and apply AI at various stages of drug development?
Industry-Academia partnerships, shared experience from startups, academia and impact assessment

Small Molecules for Immunology & Oncology

Topic: Modulating STING

Moderator: Gottfried Schroeder, PhD, Senior Scientist, Department of Quantitative Biosciences, Merck Research Labs Boston