Protein-protein interaction inhibitors
Protein-protein interactions (PPIs) are fundamental to cellular signaling and transduction which marks them as attractive therapeutic drug development targets. Once considered “undruggable” by small molecules due to their complexity, PPIs are now established as druggable targets in drug discovery. This paradigm shift provides a unique opportunity to develop novel therapies for a diverse range of conditions.
Our unique DEL – PPI Inhibitor Direct service takes advantage of our unique capability for multiplexing. The two interacting target proteins are screened in a multiplexed format and compared to monoplexed screens whereby PPI inhibitors are identified.
Service in brief
- 1. You provide the amino acid sequence of the target proteins
- 2. We conduct an expression study and provide a report
- 3. You say ”go”
- 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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Screen in multoplexed format
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Identifies PPI inhibitors
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Identifies hits and hit families
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Instant structure-activity relationship (SAR)
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Short TAT
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High success rate
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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 3 payments
- 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 proteins
- 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
- Client may nominate Chemical Series for 1 year
- Vipergen assigns its rights to Nominated Chemical Series and these becomes 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
- Kinases
- Oxidoreductase Proteases
- Hydrolases
- Isomerases
- Transferases
- Lyases
- Phosphatases
- Transcription factors
- Synthases
- E3 biquitin ligases
- Deubiquitinases (DUBs)
- Helicases
- Polymerases
- Nucleotide exchange factors
- Decarboxylases
- Ligases
- Integral membrane proteins
- G protein-coupled receptors (GPCRs)
- Ion channels
- Single-pass membrane proteins
- Nuclear receptors
- Cytosolic receptors
- Extracellular receptors
- Transcription factors
- E3 ligases
- Deubiquitinases (DUBs)
- Antibodies
- Cytokines
- Interleukins
- Growth factors
- Carrier proteins
- Adaptor proteins
- Oncoproteins
- Histone binders
- Methyl transferases
- Acetyltransferase
- Demethylases
- Deacetylases
- Viral proteins (enzymes and coat proteins)
- Bacterial proteins (enzymes and receptors)
- Fungal proteins (enzymes and receptors)