DELs in Cells – Snap – Seamless small molecule drug discovery – Get an early lead
DELs in Cells – Snap. Our easy, fast, and affordable DNA-encoded chemical library (DEL) in living cells screening service.
Service in brief
- 1. You provide the amino acid sequence of the target protein(s)
- 2. We conduct an expression studyand provide a report
- 3. You say ”go”
- 4. We conduct the screening, perform the analysis and provide a report, and chemical structure information for 25 top hits
Timelines
Expression study: 4 weeks
Screening: 4 weeks
Keys
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Screen is conducted in a living cell -
Screen is conducted using 2 screening slots (2 constructs or 2 DELs) in parallel
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Chemical structure information for 25 top hits
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More physiologically relevant conditions
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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 (>70%)
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Shorter TAT
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Identifies hits and hit families
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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
- The compensation plan comprises a total of 2 payments
- Expression Study Fee
- Screening 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 using 2 screening slots ( 2 constructs or 2 DELs)
- Vipergen delivers a hit list and report, including metrics from screens and chemical structure information for top 25 hits
- Vipergen assigns its rights for top 25 hits and these become exclusive for client
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)
| Parameter | Lib046 | Lib056 | Lib081 |
|---|---|---|---|
| Size (million of compounds) | 445 | 522 | 381 |
| Chemistries |
|
|
|
| Compounds w 1 cyclic, tertiary amide | 49% | 47% | 52% |
| Compounds w 2 cyclic, tertiary amides | – | 42% | 33% |
| Total number of building blocks (#) | 1507 | 1327 | 1138 |
| Designer building blocks (#) | 979 | 755 | 617 |
| Scaffolds (#) | 368 | 343 | 295 |
| Toxicophores (%) | 1.1 | 0.4 | 1.1 |
| Molecular weight (avg) | 612 | 529 | 525 |
| cLogP (avg) | 2.8 | 0.75 | 0.9 |
| HBA (avg) | 8.7 | 6.3 | 6.2 |
| HBD (avg) | 2.8 | 2.8 | 2.9 |
| Rotatable bonds (avg) | 10.7 | 8.8 | 8.9 |
| TPSA (avg) | 153 | 139 | 137 |
| Fsp3 (avg) | 0.5 | 0.6 | 0.6 |
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)