Assays, Biophysics And Screening Technologies

LIBRARY SCREEN (INCL. FRAGMENTS)

• Objective: Identification of binders
• Deliverables: probe displacement [%]
• Time line: up to 100,000 compounds/week
• Applications: Primary screen

TIME-RESOLVED LIBRARY SCREEN

• Objective: Identification of binders + parallel separation of slow and fast binders
• Deliverables: probe displacement [%] at 2 time points
• Time line: up to 70,000 compounds/week
• Applications: Primary screen identification of binders & separation of
• slow and fast binders

AFFINITY PROFILING

• Objective: Quantification of binding affinities
• Deliverables: Kd
• Timeline: up to 1,000 compounds/week
• Applications: Hit Profiling, orthogonal screening, lead optimization

KINETIC PROFILING (HIGH PRECISION MODE)

• Objective: Quantification of binding affinities and kinetics
• Deliverables: Kd, kon, koff, residence time
• Timeline: up to 200 compounds/week
• Applications: Hit profiling, lead optimization, candidate selection

KINETIC PROFILING (HIGH THROUGHPUT MODE)

• Objective: Identification of compounds with desired kon and residence time
• within large compound selections
• Deliverables: Clustering of kon, koff, residence time
• Timeline: up to 2,500 compounds/weeks
• Applications: Kinetic profiling of entire hit compounds sets from HTS campaigns

PROFILING OF COVALENT INHIBITORS

• Profiling of Covalent Inhibitors
• Objective: Verification of covalent bond formation, kinact & Ki quantification
• Deliverables: probe binding signal after cpd-target pre-incubation,  kinact & Ki
• Applications: Hit profiling, lead optimization

ENZYMATIC PROFILING AND NANOBRET (PROMEGA)

ENZYMATIC PROFILING

• Technologies: FI, FRET, TR- FRET, HTRF, FP, Abs, Luminescence, AlphaLisa &
• Alpha-Screen (PerkinElmer), Transcreener (BellBrook Labs), IMAP, ADP GLO (Promega) etc.
• Deliverables: IC50, Ki, Lineweaver Burk analysis, mode of action studies, enzymology
• Applications: Primary screen, hit profiling, lead optimization
• Throughput: Screen: up to 100,000 ligands/week, IC50: up to 1,000 ligands/week

NANOBRET (PROMEGA)

• Technologies: nanoBRET
• Deliverable: EC50
• Applications: Primary screen, hit profiling, lead optimization,
• cellular target engagement
• Throughput: Screen: up to 6,000 ligands/week, IC50: up to 600 ligands/week

PROFILING OF COVALENT INHIBITORS

• Objective: Verification of covalent bond formation, kinact & Ki quantification
• Deliverables: probe binding signal after cpd-target pre-incubation kinact & Ki
• Applications: Hit profiling, lead optimization

BIOPHYSICS TECHNOLOGIES AT PROTEROS

ASSAYS

• The Proteros Reporter Displacement Assay (RDA)
• Gallery Assays
• Enzymatic Profiling and NanoBRET (Promega)

BIOPHYSICS

• Surface Plasmon Resonance (SPR / Biacore 8k+)
• Isothermal Calorimetry Titration (ITC) / Malvern MicroCal PEAQ ITC
• nanoDSF (NanoTemper)
• TSA
• MicroScaleThermophoresis (MST / NanoTemper)

SCREENING

• Proteros in-house libraries in collaboration with Enamine
•  3k hand-selected Fragment library
• 41k fragment-enriched small molecules Range Finder Library
• 150k high-quality small molecule Library
• 191 k high-quality small molecule (fragment enriched) Range Finder & Small Molecule Library
• Please inquire on our DNA-encoded library options regarding our collaboration with X-Chem !

FRAGMENT LIBRARY

• 3k Proteros hand-selected fragments
• Ro3 compliant, MW 160-
• 300 g/mol, solubility
• checked
• High diversity, max
• Tanimoto similarity of 0.66
• High concentration collection (200 mM DMSO stock concentration
• -> up to 1 mM screening concentration)
• Application: Fragment screening

RANGE FINDER LIBRARY

• Fragment enriched 41k small molecules library
• Fragment enriched (25% MW
• < 300 g/mol
• Sorted by size: 10,000 Fragments
• can be screened separately
• High sp3 fraction,
• average sp3 fraction = 0.42
• Applications:
• Combination of fragment and small molecule screen
• Screen of smaller library with high hit rates.

SMALL MOLECULE LIBRARY

• 150k high-quality small molecules
• High diversity
• Specific clustering concept (23,598 clusters, mean cluster size = 6)
• Additional cluster members available by expansion into full range of Enamine compounds
• Application: HTS

RANGE FINDER & SMALL MOLECULE LIBRARY

• 191k high-quality small molecules (fragment enriched)
• Combination of range finder and small molecule diversity library
• Application: HTS

PARTNERSHIP WITH X-CHEM ON DNA-ENCODED LIBRARIES

• Please inquire !