Conference Day One
7:30 am Registration & Coffee
8:15 am Chairman’s Opening Remarks
Discovery Day: Building Cutting Edge Tools, Uncovering New Targets & Assessing the Feasibility of Candidates to Build the Next Generation of Kinase Drugs
Assay Development, Kinome Exploration & Kinase-Focussed Drug Discovery Principles
8:30 am Voruciclib, a CDK9 inhibitor, Downregulates MYC and MCL1 and Inhibits Proliferation in Heme and Solid Tumor Models
Synopsis
- Targeting transcription and phosphorylation-mediated protein degradation as an indirect mechanism to downregulate MYC and MCL1
- Voruciclib synergizes with KRAS G12C and BCL2 inhibitors in preclinical solid tumor and heme malignancy models
- Voruciclib, in combination with venetoclax, is under clinical investigation in AML
9:00 am Drug Screening with the Gold-standard Assay Against the Largest Kinome Available Reveals Unexpected Drug-Enzyme Relationships
Synopsis
- Mono-specificity is difficult to achieve and rarer than advertised
- WT versus mutant and phosphorylation status matter greatly
- Multiple assays are required for a complete pre-clinical assessment
9:30 am Understanding the Global Atlas of Motifs for the Human Protein Kinome
Synopsis
- Experimental profiling of kinases
- Computational application and evaluation of performance
- Illumination of MS phosphoproteomics data
10:00 am Morning Refreshments & Speed Networking
11:00 am Discovery and Validation of Biomarkers for Patient Stratification
Synopsis
- Identification of predictive drug response biomarkers by Oncolines® cancer cell panel profiling
- Comparative profiling of small molecule oncology drugs to identify biochemical mechanism of action
- Validation of drug response biomarkers in disease models and in proof-of concept clinical studies
11:15 am [VIRTUAL] Automated High-Throughput Analysis of Non-Equilibrium Inhibition In Kinase Inhibitor Discovery
Synopsis
- Discovering kinase inhibitors with non-equilibrium modalities to increase the residence time and possible decoupling of pharmacokinetics and pharmacodynamics.
- High-throughput analysis of kinetic data for slow-onset inhibitors
- High-throughput analysis of kinetic kinact/KI data for irreversible inhibitors
11:45 am Exposing Novel Kinase Polypharmacology and Drug Escape Mechanisms in Cells With NanoBRET
Synopsis
- Enabling live cell kinase profiling: Exploring the landscape of DDR kinase inhibitors in cells
- Kinome-wide live cell profiling reveals novel interactions for type II kinase inhibitors
- Protomer selectivity of RAF dimer inhibitors informs on the mechanism of inhibition within the RAS-RAF signalosome
12:15 pm Enzymatic Assays for Kinase Inhibitor Discovery
Synopsis
- Enzymatic assays drive kinase inhibitor discovery programs
- Multiple assay formats and readouts are available, but some have distinct advantages
- Mass spectrometry is an underutilized tool for kinase inhibitor assays, but has great potential
12:45 pm Lunch Break
1:45 pm Building Ultralarge Next Generation Libraries for the Discovery of Novel and Selective Kinase Inhibitors
Synopsis
- Novel libraries to expand the searchable chemical space for kinases
- Specific challenges of kinase inhibitors for brain penetration and selectivity and the importance of multiparameter optimization
- Robotic synthesis and automation of assays to support AI drug discovery
2:15 pm Monitoring Continuous Enzyme Activity with Fluorogenic Sensor Assays Enables Data-Rich Decisions for Improved Kinase & Phosphatase Drug Discovery
Synopsis
- Advantages of PhosphoSens® technology as a continuous activity assay (a progress curve in every well)
- Kinome selectivity profiling at low or high ATP with insight into compound dependent kinetics and MOA
- Deep characterization of kinase inhibitor potency for reversible or irreversible inhibitors
2:45 pm The Future is Here: Automation Demonstrates its Value as a Precision Tool for Accelerating Drug Discovery
Synopsis
- Robotics-enabled process for inhibitor profiling, providing an unparalleled depth of data capture, going beyond the current state-of-the-art of biochemical assay setup
- 9 orders of magnitude range in liquid volume handling and contact-free digital dispensing for true, non-serial, independent experimentation enabling experiments to be designed exclusively for each molecule
- Differentiated triage strategies enable data utilization to support machine learning and more traditional hit discovery activities for program progression – no more single-shot screening!
3:15 pm Afternoon Break & Poster Session
Inhibitor or PROTAC – Overcoming Tumor Resistance & Improving Durability
4:00 pm [VIRTUAL] Degradation Is Not Always Superior to Enzymatic Inhibition: Lessons Learned from EGFR Heterobifunctional Degraders
Synopsis
- Targeted degradation of EGFR failed to suppress resistance common to EGFR targeted therapies
- Degradation resulted in decreased efficacy relative to non-degrader controls
- Comparing degrader vs non-degrader controls highlighted an unexpected role for ER stress contributing to the efficacy of canonical EGFR targeted therapies
4:30 pm Full Audience Activity – Roundtable Discussion
Synopsis
At your table discuss the following questions:
- What are the 3 most important factors to consider when selecting your modality of choice?
- In your mind, what are the central pros of a PROTAC degrader vs a traditional inhibitor?
- What feature would you prioritize as your ‘dealbreaker’ when making a final decision regarding modality?