Validation tools 
for targeted
protein degradation

Clypse-Open is a core facility of Kiel University that offers purpose-built assay services for developers of degrader molecules.
RiPA, HiBiT and NanoBRET platforms delivering quantitative, publication-quality data.

3
Assay Platforms
6+
Years Research
ERC
Funded Origins
The Science

Why degraders?

Classical inhibitors can only block proteins with accessible active sites. Degrader molecules recruit the cell's own degradation machinery to eliminate target proteins entirely, including transcription factors and other non-enzymatic targets previously considered undruggable.

Moreover, a single degrader molecule acts catalytically, driving multiple rounds of target degradation. The degrader landscape spans several modality classes shown on the right — Clypse-Open offers dedicated assay platforms covering critical validation steps from ternary complex formation to intracellular degradation kinetics.

Our assay platforms →
Degrader Classes
01 — Proteolysis-Targeting Chimeras (PROTACs)
Bivalent small molecules that form a ternary complex between a target protein and an E3 ubiquitin ligase, driving proteasomal degradation.
02 — Molecular Glues
Stabilise a neo-interaction between a target and E3 ligase without a traditional linker-warhead architecture.
03 — Biologic Degraders
Bivalent biologics combining antibody-mediated targeting with lysosomal degradation, enabling membrane and extracellular targets.
Our Assay Platforms

Multiple assays, one focus – for all types of degraders

01 RiPA
Rapamycin-induced proximity assay
The RiPA assay allows for the expression of E3 ligases and targets in cells. Rapamycin-induced dimerization allows the identification of ideal E3 ligases for every target of interest (Adhikari et al, eLife, 2024).
Best E3 ligase–target pairs MedChem-free
Learn more ->
02 HiBiT
Live-cell protein degradation assay
Lentiviral expression of your protein of interest combined with the HiBiT assay is a sensitive, high-throughput method for validating and optimizing degraders. It allows you to rapidly measure target protein degradation in living cells by tracking the depletion of a tagged protein.
DC50 / Dmax
Learn more ->
03 NanoBRET
Nano Bioluminescence Resonance Energy Transfer
The NanoBRET assay is a powerful, live-cell tool used to measure how well a degrader enters cells (permeability) and binds to its target protein (target engagement).
BRET Cell Permeability Target Engagement
Learn more ->
Working with Us

How we collaborate

01
Scientific Consulting
We work with you to identify the right assay platform and experimental design for your specific target, E3 ligase, and/or degrader from the outset.
02
Flexible Engagement
Every project is scoped to your needs — from a focused single-assay pilot to a multi-target program. We share interim results, refine the experimental approach together, and close with a structured data package.
03
Publication
Results generated using Clypse-Open tools may be freely published. Academic collaborations are governed by a Material Transfer Agreement.
6+
Years degrader Research
About Clypse-Open

Built by scientists, for degrader developers

The core facility Clypse-Open emerged from the Tumor Biochemistry working group at the Biochemical Institute of Kiel University. Our Clypse-Open assay platforms were developed as part of ERC-funded research programs and are now available to external academic partners.

We partner with academic groups, pharmaceutical companies and biotechs to provide rigorous, publication-quality data at every stage of degrader research.

Work with us
Our Team

Meet the team

AG
Dr. Anneli Gebhardt
Scientific Lead
Scientific Lead
YG
Dr. Yiliam Cruz Garcia
Sci. Associate
Scientific Associate
LinkedIn
EW
Prof. Dr. Elmar Wolf
Scientific Consultant
Scientific Consultant
LinkedIn
AK
Dr. Anneke Kramm
Managing Director
Managing Director
LinkedIn
Science

Selected Publications

2026
O'Hanlon JA, Gutsche K, Müller JE, Ranjan Prusty N et al., Wolf E, Newton GK, Evans LE.
Journal of Medicinal Chemistry, 2026
Degrader
2025
Miletic N, Weckesser J, Mosler T et al., Wolf E, Dikic I, Knapp S.
ACS Chemical Biology, 2025
E3 Ligase
2025
Wagner K, Keiten-Schmitz J, Adhikari B, Patra U et al., Wolf E, Müller S.
Nature Chemical Biology, 2025
Proximity
2024
Adhikari B, Schneider K, Diebold M, Sotriffer C, Wolf E.
eLife, 2024
RiPA
2024
Sflakidou E, Adhikari B, Siokatas C, Wolf E, Sarli V.
ACS Pharmacology and Translational Science, 2024
Degrader
2022
Solvie D, Baluapuri A, Uhl L, Fleischhauer D et al., Wolf E, Eilers M.
Nature, 2022
MYC
2021
Dolle A, Adhikari B, Kramer A, Weckesser J et al., Wolf E, Knapp S.
Journal of Medicinal Chemistry, 2021
Degrader
2020
Adhikari B, Bozilovic J, Diebold M et al., Wolf E.
Nature Chemical Biology, 2020
Degrader
Compliance

Regulatory Framework

Cell Lines
Cell Line Usage
All human-derived cell lines are sourced from ATCC, DSMZ and ECACC. STR profiling and mycoplasma testing are performed routinely. Containment complies with EU Directive 2009/41/EC and German GenTSV guidelines. In-house cell lines are governed by a Material Transfer Agreement.
In Vivo
Animal Studies
In vivo studies are conducted only where scientifically necessary, in full compliance with EU Directive 2010/63/EU, implemented in Germany via TierSchG and TierSchVersV. All protocols are approved by the responsible authority prior to commencement.
GDPR
Data Protection
Client data is handled in accordance with GDPR / DS-GVO. Data processing agreements are available on request. No client data is shared with third parties without explicit written consent.
GLP
Quality Standards
Studies follow Good Laboratory Practice principles. SOPs, calibration records and raw data are archived and available for client audit on request.
Get in Touch

Request a quote or consultation

Tell us about your degrader program and we will respond within two business days with a proposed assay plan and indicative timeline.

Email
info@clypse-open.com
Location
Kiel, Germany

By submitting this form you agree to our Datenschutzerklärung.

Thank you for your enquiry.

We will be in touch within two business days.

RiPA

Rapamycin-induced proximity assay
Overview

Rapamycin induced proximity assay that allows the expression of E3 ligase target pairs in cells.

Based on the rapamycin-induced proximity assay (RiPA) framework published in eLife (2024), the platform is ideally suited for E3 ligase pair validation before investing in more complex cellular models.

How it works

E3 ligase-FRB constructs and FKBP12- and luciferase tagged target constructs are generated and transfected into cells. Rapamycin treatment leads to dimerization of FRB and FKBP12 tags and thus induces proximity between the E3 ligase and the target. Subsequently, E3 ligase induced target degradation can be measured by luciferase activity. RiPA is a quantitative and scalable cellular assay that predicts the suitability of E3 ligases for a specific target.

E3 LIGASE FRB + TARGET Luc FKBP12 SEPARATED Rapamycin E3 LIGASE FRB TARGET Luc FKBP12 TERNARY COMPLEX READOUT Immunoblotting or Luciferase activity
Adapted from Adhikari et al., eLife 2024 (CC BY 4.0)
You provide
cDNA of your target
You receive
Degradation %
E3 ligase comparison
Suitability ranking
Best E3 ligase–target pairs MedChem-free
Interested in RiPA?

Request a quote or consultation

Tell us about your target and E3 ligase pair and we will respond within two business days.

Run My Assay
02 — Live-cell Degradation

HiBiT

Live-cell protein degradation assay
Overview

The HiBiT assay is combined with lentiviral expression of your protein of interest tagged with the 11-amino acid HiBiT peptide. When combined with its complementary partner LgBiT, HiBiT reconstitutes a highly active, functional luciferase enzyme, generating a luminescent signal directly proportional to target protein abundance.

How it works

The target of interest (with a C-terminal or N-terminal HiBiT tag) is cloned into a lentiviral expression vector. The desired cellular model is transduced with the lentivirus carrying the target, followed by antibiotic selection. The established cellular system can be used to evaluate target degradation upon degrader treatment. The larger LgBiT fragment is introduced to the cells along with luciferase substrate. The intensity of the light is directly proportional to the amount of overexpressed HiBiT-tagged protein and thereby allows for evaluation of degradation.

You provide
cDNA of your target
You receive
HiBiT-tagged cell line
Positive control
DC50 / Dmax
Interested in HiBiT?

Request a quote or consultation

Tell us about your target protein and degrader compound and we will respond within two business days.

Contact Us
03 — Live-cell Ternary Complex

NanoBRET

Target Engagement Assay
Overview

Target engagement and cell permeation are crucial parameters that may limit the efficacy of degraders. Here, the target protein is tagged with a NanoLuc luciferase. When a cell-permeable, fluorescently labeled tracer binds the target, it triggers a bioluminescence resonance energy transfer (BRET). Unlabeled potential binders are added to the cells competing for the target and successful binding causes a dose-dependent decrease in the BRET signal.

How it works

A luciferase-tagged target is in a dynamic equilibrium with a fluorescent reporter, a tracer, occupying a known ligand interface. Upon addition of the unlabeled potential binder,, target engagement results in competitive displacement of the tracer and dose-dependent loss of the BRET signal. Comparing target engagement in both live and permeabilized cells allows to assess the intracellular availability of the binder.

You provide
cDNA of your target
You receive
Luciferase-tagged cell line
Positive control
Ternary complex BRET Target engagement
Interested in NanoBRET?

Request a quote or consultation

Tell us about your target, E3 ligase and degrader compound and we will respond within two business days.

Contact Us

Datenschutzerklärung

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Verantwortlich fuer die Datenverarbeitung auf dieser Website ist: E3Clypse GmbH, Kiel, Deutschland. E-Mail: info@e3clypse.com

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Regulatory Compliance

Cell Line Authentication and Containment

All cell lines are sourced from authenticated biorepositories including ATCC, DSMZ and ECACC. Routine STR profiling and mycoplasma screening ensure cell line integrity. In-house cell lines are governed by a Material Transfer Agreement and may be freely used in publications, with co-authorship of the contributing Clypse-Open scientists as a prerequisite. Work with genetically modified cell lines complies with EU Directive 2009/41/EC and the German GenTG and GenTSV.

Animal Studies

Clypse-Open applies the 3Rs principles (Replacement, Reduction, Refinement). All animal studies are conducted in full compliance with:

All protocols are approved by the competent authority in Schleswig-Holstein prior to commencement.

GLP and Data Integrity

Studies follow Good Laboratory Practice (GLP) principles. All SOPs, calibration records and raw data are archived in a controlled document management system and available for client audit on request.

Impressum

Angaben gemäß § 5 TMG

Biochemisches Institut an der CAU Kiel
Rudolf-Höber-Str. 1
D-24118 Kiel
Deutschland

Kontakt

E-Mail: info@clypse-open.com

Geschäftsführung

Dr. Anneke Kramm

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