DELs in Cells – Integral Membrane Proteins – Seamless small molecule drug discovery – Get an early lead
DELs in Cells service for integral membrane proteins with emphasis on high success rate, short turn-around-time, high quality data and low false positive rate.
Integral membrane proteins
Integral membrane proteins, such as G protein-coupled receptors (GPCRs) and Ion channels perform numerous biological functions. However, ligand discovery for membrane proteins is highly challenging, because a natural cellular environment is often necessary to maintain protein structure and function.
Our unique DEL – Integral Membrane Protein service takes advantage of our unique capability for screening inside a living cell thus providing the natural screening conditions.
Service in brief
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1. You provide the amino acid sequence of the target protein(s)
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2. We conduct an expression 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
Expression study: 4 weeks
Screening: 4 weeks
Keys
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Screen is conducted in a living cell -
More physiologically relevant conditions
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Membrane protein screened from the cytosolic side
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Lower attrition rate (assumed)
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Broader target space – no need for purified target protein
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High success rate (>80%)
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Short TAT
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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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Instant MOA of hits by screening in the presence of a known ligand or resynthesized hit
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Large scale project with cost reduction by multiplexing (unique capability)
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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 (no structural information required)
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Straightforward and transparent data analysis
Business Model
- Simple fee-based plan with no reach-through and royalty payments
- Hit exclusivity and transparent cost structure – Client owns all hits and foreground IP without any downstream financial obligations
- The compensation plan comprises a total of 3 payments as a transparent cost structure
- Pre-Project Expression 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 amino acid sequence for the target protein
- Vipergen performs the Expression Study (go-no-go)
- Vipergen performs one round of screenings with varying constructs and different libraries.
- 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
- Vipergen can assist in off-DNA resynthesis as a fee-for-service
- Client may nominate Chemical Series for 1 year
- Vipergen assigns its rights to Nominated Chemical Series, and these become exclusive for you as a client
- Client own all foreground IP, data and hits of nominated series without royalty payment or other downstream financial obligations
DELs
Vipergen’s high fidelity DELs are synthesized using robust chemistry and with a purification step 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)