8:00 am Registration & Networking Coffee

8:50 am Chair’s Opening Remarks

  • Nick Shah Head of In Vitro Pharmacology, DiCE Molecules

Utilizing Next-Generation Chemical Biology Platforms for Novel Target Identification

9:00 am Application of Chemical Biology Probes and Bioorthogonal Chemistry in Drug Discovery

Synopsis

  • Several examples of how chemical biology probes and bioorthogonal chemistry were used for target identification and engagement, selectivity profiling (offtargets) and mechanism of action studies in drug discovery projects
  • Several different types of chemical biology probes were utilized including enzyme class-specific activity-based probes, cysteine-specific reactivity-based probes as well as target-specific clickable  covalent inhibitor and photoaffinity probes
  • These probes proved to be invaluable for assessing target engagement, identifying off-targets and expanding of knowledge of the target biology

9:30 am A High-Throughput, Mass Spectrometry-Based Proteomics Platform for Rapid Drug Perturbation Profiling

Synopsis

  • Development of a high throughput and automation-compatible mass spectrometry-based proteomics workflow for rapid cellular drug perturbation profiling
  • Sharing examples on how the platform can support MoA de-convolution of chemical matter from phenotypic screens to identify novel drug targets
  • Examples on how the platform can support the identification of novel protein degrader targets

10:00 am Monitoring Dynamics of Protein Degradation in Living Cells

Synopsis

  • Three case studies of PROTAC mechanism of action in different systems
  • The Degradogram: Live cell kinetic degradation profiles and quantitative analysis
  • Relationship of cellular ternary complex formation and ubiquitination to degradation rate
  • HTS screening of compounds in cellular assays

10:30 am Speed Networking & Morning Refreshments

11:30 am Finding the Needle in the Haystack: Learnings in Integrated Lead Discovery

Synopsis

  • No single assay will find all of the hits, all of the time, so how does one pick the “right” assay for a new lead discovery campaign? Robust identification and characterization of chemical starting points requires well-validated and predictive biochemical, biophysical, and cellular assays
  • There are significant benefits in combining multiple screening approaches, whether concurrently or iteratively, to discover novel chemical matter modulating targets. Integrated Lead Discovery enables synergy between key hit finding approaches and allows for the detection of unexpected modes of action and serendipity
  • Vignettes of integrated lead discovery campaigns that led to chemical starting points for advanced leads and drug candidates will be shared

12:00 pm The New Age of Discovery: Harnessing Chemoproteomics for Small Molecule Drug Design

Synopsis

  • Proteomics is now recognized as an essential hypothesis generating tool for every stage of the drug design process
  • A suite of chemoproteomic strategies provide valuable insights into drug discovery programs
  • Cellular thermal shift assays are a compound class agnostic means of determining target engagement and selectivity

12:30 pm Networking Lunch

Expanding the Druggable Proteome Through Next-Generation Screening Platforms

1:30 pm Predicting Small Molecule Tractability of Novel Targets to Prioritize and Accelerate Hit Identification Activities

Synopsis

  • Advances in both genome-wide screening and genome-wide analyses have enabled the identification of numerous putative therapeutically relevant targets for hit identification programs. Pursuing all of these targets in small molecule hit ID programs is neither feasible nor warranted
  • Integrating both in silico and experimental methods to rapidly predict the small molecule tractability of novel targets
  • Experimentally we utilize multiple affinity-based screening platforms, including ELT and ASMS, to quickly prioritize novel therapeutically relevant targets based on empirical data and focus small molecule hit identification efforts on those that are most likely to succeed

2:00 pm PROTEINi: A Unique Approach to Expand Druggable Space

Synopsis

  • Our current concept of druggable space is finite, and genetic approaches to target discovery do not operate at the level of target engagement
  • PROTEINi uses peptide ligands in phenotypic assays to identify and de-risk new targets
  • PhoreMost has deployed PROTEINi in multiple TAs, thereby establishing a drug discovery pipeline

2:30 pm Enabling Drug Discovery for the PARP Protein Family through the Detection of Mono-ADP-Ribosylation

Synopsis

  • Ribon is targeting the family of monoPARPs which, unlike PARP1/2, only add a single ADP-ribosyl-moiety onto their substrates
  • Strategies to measure poly-ADP-ribosylation used in the development of PARP1/2 inhibitors are unable to detect the modification catalysed by monoPARPs
  • We identified antibodies that detect ADP-ribosylation by monoPARPs which we use to assess the potency of small molecules and for biological screens

3:00 pm Afternoon Refreshments & Poster Session

Leveraging Innovative Chemical Probes to Accelerate Fragment-Based Lead Generation

4:00 pm Covalent Inhibitor Discovery by Electrophile Fragment Screening

  • Nir London Senior Scientist, The Weizmann Institute of Science

Synopsis

  • Presenting an electrophilic fragment screening approach that can be applied to a wide range of targets
  • Discussing a high-throughput reactivity assay and cumulative screening data against a large panel of targets allows us to focus on recognition-based hits, and eliminate promiscuous compounds with high reactivity
  • In combination with high-throughput crystallography, this approach enabled us to find potent and selective covalent probes against several targets for which no previous probes were available

4:30 pm SAR by 19F NMR: Using Protein-Observed Fluorine NMR for Targeting Epigenetic Protein Complexes

Synopsis

  • Protein-observed fluorine NMR is a valuable FBLD tool for generating fragment leads for protein-protein interactions
  • 3D fragments can lead to selective inhibitors for bromodomain-containing proteins
  • Simultaneous screening of multiple proteins by protein-observed fluorine NMR has led to development of a BRD4 domain 1 selective chemical probe

5:00 pm Interactive Round Table Discussions

Our breakout roundtables will allow you to have more intimate and open discussions on some of the hottest topics and key areas of debate. Drive your own learning, crowd-source ideas and get inspired. Immerse yourself in the following discussions:

Serendipity versus rational drug design: How new chemical approaches might provide opportunities for overcoming the undruggable nature of desirable targets?

How to rapidly and successfully discover and exploit novel targets beyond oncology using current tools in the toolbox?

How to overcome the chemical, biological, and computational challenges in the development of inhibitors targeting protein-protein interactions?

5:30 pm Chair’s Closing Remarks & End of Day One