CONFERENCE DAY ONE
Wednesday, December 11, 2024
8:00 am Check-In & Light Breakfast
8:50 am Chair’s Opening Remarks
Streamlining Hit Generation with High-Throughput & Unbiased Covalent Screens to Define Innovative Warheads for Hard-to-Drug Targets
9:00 am Covalency Offers Unique Opportunities for Difficult Targets
Synopsis
- Covalency provides opportunities for difficult drug targets
- Screening identifies a starting point for a TF target
- Proteomics is an essential tool for covalency focused efforts
9:30 am Mass Spectrometry Screening & Hit Optimization Strategies for Efficient Covalent Drug Discovery
Synopsis
- Maximizing throughput for MS-based covalent screens
- Integrating data generated from MS screens to identify potent and selective hit compounds
- Triaging hits to identify the most tractable compounds
10:00 am Panel Discussion: Debating Systematic & Scalable Screening Methods to Rationally Discover & Develop Covalent Handles with Optimized Reactivity & Selectivity
Synopsis
- What are the best methods for finding tractable hits?
- How can we streamline hit-to-lead optimizations?
11:00 am Morning Break & Speed Networking
Synopsis
Our speed networking session is the ideal opportunity to get face-to-face time with many of the brightest minds working to discover and develop covalent modalities. Introduce yourself to the attendees that you would like to have more in-depth conversations with, benchmark against industry leaders, and establish meaningful business relationships that you can pursue for the rest of the conference and beyond
11:30 am DNA-Encoded Library Technology- A Catalyst for Covalent Ligand Discovery
Synopsis
- DNA-encoded libraries are massively diverse collections of drug-like molecules which afford a facile opportunity to identify ligands for small molecule drug discovery and development. We will review applications of these libraries to successfully identify novel chemical equity to protein targets, including KRas G12C and BTK
- X-Chem’s covalent DNA-Encoded Library (DEL) collection integrates learnings from FDA-approved covalent drugs, coupled with optimized covalent screening workflows, to support de novo hit discovery for challenging drug targets. Covalent DELs incorporate diverse warhead elements of varying reactivities and preferred amino acid engagement, providing a truly unbiased collection of ligands for early-stage covalent hit identification.
- Data-rich DEL outputs power computational strategies to maximize SAR information and propel hit candidates into actionable drug leads
Accelerating the Development of Unbiased & Scalable Platforms to Access & De-Risk Novel Chemistry Amenable for Covalency & Propel Discovery Pipelines
12:00 pm Practical Approaches to Accelerate Covalent Drug Discovery
Synopsis
- Exploring early profiling and selection of actionable targets
- Assessing hits to predict target traceability
- Enabling biochemical and chemoproteomics assays to build programs
12:30 pm Mechanistic Study of Reversible & Irreversible Covalent Inhibitors
Synopsis
- The emergence of reversible covalency addresses off-target safety concerns, countering challenges posed by irreversible covalent inhibitors. Yet, characterization of this novel mechanism is hindered by limited assays and tools
- Establishing enzyme kinetic assays, incorporating slow binding Ki Kinact measurement and jump dilution to enable the determination and differentiation of reversible from irreversible covalency mechanism
1:00 pm Unveiling WuXi AppTec’s Innovative Approaches in the Identification of Covalent Small Molecule Binders
Synopsis
- Innovative approaches for covalent hit finding
- Integrated downstream validation methods
- WuXi AppTec offers comprehensive target-to-lead services
1:30 pm Lunch Break & Networking
Spearheading the Specific Covalent Targeting of More Abundant Residues Beyond Cysteine to Access Novel Binding Pockets & Expand the Druggable Proteome
2:30 pm Specific Covalent Targeting of Histidine, Tyrosine & Lysine to Expand the Druggable Proteome
Synopsis
- Development of novel warheads for covalent screening of histidine, tyrosine and lysine residues
- Enhancing the capture and mass spectrometry detection of sensitive peptide-ligand pairs
- Integration of structural information to prioritize novel binding pockets for further development of covalent or non-covalent compounds
3:00 pm Targeting of Histidine Residues to Increase the Pool of Potential Targets Amendable for Covalent Drug Discovery
Synopsis
- Showcasing how to identify and map histidine residues across a wide range of proteins to determine their potential as covalent drug targets
- How to marry the right electrophiles with histidine moieties
- Ligand-first versus electrophile-first approaches to target Histidine residues
3:30 pm Afternoon Networking Break
Advancing Chemoproteomic Platforms & Probes to Better Interrogate Novel Biology & Amplify the Druggable Proteome Outside Oncology
4:00 pm Towards a Chemical Biology Platform for the Systematic Discovery & Evaluation of Novel Covalent Chemistry
Synopsis
- Exploring insights into flexible library setup to synthesis novel covalent warhead libraries
- Showcasing MS and proteomics-based discovery and profiling assays for novel covalent warhead motifs
- Examining setups to screen and profile novel covalent libraries
4:30 pm Roundtable Discussion: Fueling the Covalency Renaissance by Strategizing the Chemistry Toolbox to Target Residues Beyond Cysteine with Orthogonal Reactivity
Synopsis
- Which amino acids are seen as the next frontier in covalent drug discovery?
- What is the mass spectrometry or alternative screening toolbox for other amino acids?
- How can we build drug-like warheads that hit other side chains? Should we be screening these more promiscuous warheads?
- What pre-clinical safety and ADME data would give you confidence to use these chemotypes in your own projects?
5:00 pm Covalent Fragment-Based Ligand Discovery to Drug Refractory Targets
Synopsis
- How can covalent fragment-based ligand discovery be leveraged to tackle so-called undruggable targets?
- What are the advantages of a target-centric approach to covalent fragment-based ligand discovery?
- What approaches (biochemical and cell-based) can be deployed to progress covalent fragment starting points to mature lead molecules within a drug discovery campaign?
5:30 pm Chairs Closing Remarks
5:35 pm End of Conference Day One
ACCESS THE FULL PROGRAM
Explore three days of sessions and workshops, the full 22+ speaker faculty, and more by downloading your copy of the event guide.
