Selectivity in drug discovery
A major challenge in drug discovery is finding selective ligands that modulate the target without modulating other targets associated with toxicity or undesirable side effects.
Our unique DEL – Selectivity Direct service takes advantage of our unique capability for multiplexing. The target and anti-target(s) proteins are screened in a multiplexed format whereby target selective hits are identified.
Service in brief
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1. You provide the purified target protein and anti-target protein(s) (micrograms)
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2. We conduct a feasibility study and provide a report
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3. You say ”go”
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4. We conduct the screening, perform the analysis and provide a report, including hit list with chemical structure information
Timelines
Feasibility study: 4 weeks
Screening: 4 weeks
Keys
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Screen requires small quantities of purified target and anti-target(s) proteins (micrograms) -
Screen is conducted multiplexed
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Screen is conducted with many conditions in parallel
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Screen is conducted in a homogeneous assay to avoid matrix binders and target denaturation
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Identifies hits and hit families
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Instant structure-activity relationship (SAR)
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Instant selectivity/specificity of hits by multiplexed screen against target and anti- targets (unique capability)
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High success rate (>75%)
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Low false positive rates (100% match between DNA code and compound)
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Applicable across disease areas and target classes
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Demonstrated ability to address targets considered difficult, including transcription factors, protein complexes, solubilized membrane proteins and PPI targets
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Straight forward and transparent data analysis
Business Model
- Simple fee-based plan with no reach-through and royalty payments
- Hit exclusivity
- The compensation plan comprises a total of 3 payments
- Pre-Project Feasibility Study Fee – scales with work
- Screening Fee – scales with screening slots
- Chemical Series Nomination Fee
- The project flow is rapid and straightforward:
- Client provides the target protein (100 micrograms)
- Vipergen performs Feasibility Study (go-no-go)
- Vipergen performs one or two rounds of screening, each under varying conditions and with different libraries.
- After each screening round, Vipergen delivers a hit list and report, including metrics from screens and chemical structure information
- Hits are reserved for client for 1 year
- Client may resynthesize and test hits in relevant assays and use data for 1 year
- Client may nominate Chemical Series for 1 year
- Vipergen assigns its rights to Nominated Chemical Series and these become exclusive for client
DELs
Vipergen’s high fidelity DELs are synthesized using robust chemistry and with a purification
steps after each chemical transformation, thus providing 100% correspondence between
code and compound (no truncates).
Key drivers for library design
- Chemical diversity
- Physicochemical properties
- Fidelity
- Hit resynthesis (off DNA)
Target classes
Our streamlined DNA-encoded chemical library (DEL) screening service for purified proteins has successfully delivered hits and leads against numerous target classes. Including:
Enzymes
- Kinases
- Oxidoreductase Proteases
- Hydrolases
- Isomerases
- Transferases
- Lyases
- Phosphatases
- Transcription factors
- Synthases
- E3 biquitin ligases
- Deubiquitinases (DUBs)
- Helicases
- Polymerases
- Nucleotide exchange factors
- Decarboxylases
- Ligases
Membrane proteins
- Integral membrane proteins
- G protein-coupled receptors (GPCRs)
- Ion channels
- Single-pass membrane proteins
Receptors
- Nuclear receptors
- Cytosolic receptors
- Extracellular receptors
Protein-protein interaction targets
- Transcription factors
- E3 ligases
- Deubiquitinases (DUBs)
- Antibodies
- Cytokines
- Interleukins
- Growth factors
- Carrier proteins
- Adaptor proteins
- Oncoproteins
Epigenetic targets
- Histone binders
- Methyl transferases
- Acetyltransferase
- Demethylases
- Deacetylases
Pathogenic targets
- Viral proteins (enzymes and coat proteins)
- Bacterial proteins (enzymes and receptors)
- Fungal proteins (enzymes and receptors)