DELs in Cells – Molecular Glue Direct – Tap into the potential of molecular glue
Molecular glues in targeted protein degradation
Unlocking the potential of targeted protein degradation (TPD) through the cellular ubiquitin-proteasome machinery represents a paradigm shift in drug discovery, broadening the scope of druggable targets. This process involves stabilizing a complex between the protein of interest (POI) and one of the 600+ E3 ubiquitin ligases encoded by the human genome, promoting POI ubiquitination and subsequent degradation.
The TPD field has been spearheaded by heterobifunctionals, such as PROTACS, whereas only a limited set of molecular glues have been discovered and advanced. Heterobifunctionals are easier to discover but more difficult to advance due to their size/physiochemical properties and the “hook effect”. In contrast molecular glues are more difficult to discover but easier to advance due to their better physicochemical properties and mode of action.
Our unique DEL – Molecular Glue Direct service takes advantage of our unique capability for multiplexing. POI(s) and E3 ubiquitin ligase(s) are screened in a multiplexed format and compared to the monoplexed screens.
Service in brief
- 1. You provide the amino acid sequence for the target protein(s) and choose E3 ubiquitin ligase(s)
- 2. We conduct an expression and a co-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: 4-8 weeks
Keys
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Screen is conducted in a living cell
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More physiologically relevant conditions
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Screen is conducted multiplexed: POI(s) and E3 ubiquitin ligase(s)
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Identifies molecular glue directly
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Identifies hits and hit families
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Instant structure-activity relationship (SAR)
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Success rate 25-30%
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To mitigate the relatively low success rate most molecular glue projects have either multiple targets or multiple E3 ubiquitin ligases
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Applicable across disease areas and target classes (no structural information required)
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Demonstrated ability to address targets considered difficult, including transcription factors, protein complexes, and PPI targets
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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 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 microgram)
- 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 becomes exclusive for client
Screening for molecular glues principle
DELs in Cells – Molecular Glue Direct enables the discovery of molecular glue molecules by screening the POI(s) in a living cell, using our cellular Binder Trap Enrichment (cBTE) technology in our unique multiplexed format.
The multiplexing capability allows for the simultaneous screening of multiple proteins, including a POI and an E3 ligase, in the same living cell. This is achieved by tagging each target protein with barcoding DNA, and using the barcode to enable the discovery of compounds binding to the POI, the E3 ligase, and the complex between them, respectively.
In the subsequent analysis, molecular glues are identified as the molecules that are found as shared hits between the POI and the E3 ligase.
The multiplexing cBTE technology can also be used for identifying molecular glues in more general cases, where the interaction partners do not include an E3 ligase, and can even be used to identify inhibitors of protein-protein interaction directly.

DELs in Cells – Molecular Glue Direct screen. DEL and target binding DNA (Bait-DNA) are co-injected, binding allowed to take place, and the DNA ligated in emulsion. Molecular glue hits are observed as shared hits between the POI and the E3 ligase.
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)
Parameter | Lib046 | Lib056 | Lib081 |
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Size (million of compounds) | 445 | 522 | 381 |
Chemistries |
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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)
Technical information
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