Proteros - Qualified Hits Technologies

DISCOVER:

• Mode of Inhibition - Whether allosteric, orthosteric or covalent
• Affinity - We measure KD, ligand efficiency and IC50.
• Binding Kinetics - Essential binding kinetics such as Kon, Koff and residence time.
• Selectivity - Determine the KD as well as off target interaction analysis.
• Binding mode - Use either X-ray crystallography or Cryo-EM to structurally determine the binding mode.

ANALYSIS AND PLANNING

• Team Assembly
• Target access assessment
• Target analysis
• HTS library selection
• Screening cascade defined
• Assays identified
• Structural biology planning

PLATFORM ESTABLISHMENT

• Establishment of protein production
• Establishment of assay systems
• Establishment of structural biology
• LIBRARY SCREENING
• Fragment screening
• [3k hand-picked fragments]
• Range Finder screening
• [fragment enriched 41k small molecule library]
• Small molecule HTS
• [150k high-quality small molecules]
• Reporter Displacement
• Enzymatic Assays
• SPR, MST, nanoDSF, nanoBRET, TSA

HIT CONFIRMATION

• Reporter displacement assays
• Binding affinity and kinetic profiling via SPR
• Enzymatic profiling of impact of inhibitors
• MicroScale Thermophoresis binding assays
• Label-free nanoDSF binding assays
• nanoBRET target engagement
• Luminescence interaction analysis using Alpha LISA Screening
• Interaction thermodynamic analysis using Isothermal titration calorimetry

HIT CONFIRMATION

• Reporter displacement assays
• Binding affinity and kinetic profiling via SPR
• Enzymatic profiling of impact of inhibitors
• MicroScale Thermophoresis binding assays
• Label-free nanoDSF binding assays
• nanoBRET target engagement
• Luminescence interaction analysis using Alpha LISA Screening
• Interaction thermodynamic analysis using Isothermal titration calorimetry

STRUCTURAL ELUCIDATION

• X-ray crystallography
• Cryo-EM

QUALIFIED HITS

• At the end of the process you will receive the deeply characterized qualified hits,
• which meet the project specifications.