Identification of Drug-Target Interactions

Our YChemH screening platform is dedicated to identifying direct proteins targets of small bioactive molecules  and the understanding their mode of action.

Our Technology

ULTImate YChemH

The discovery of small molecule bioactives or first-in-class drugs often begins with identifying the function of possible therapeutic target(s). Our yeast three-hybrid system (Y3H) technology can support your early drug discovery program by: 

  • Elucidating Mechanism of Action of small molecule coming from a phenotypic screen, 
  • Identifying off-target interactions to anticipate side-effects of your lead compound and selection of the best clinical candidate and
  • Drug repurposing to identify new therapeutic use(s) of an existing drug.

Our Technology

ULTImate YChemH

Our ULTImate YChemH™ is a modified version of our Y2H system that enables the identification of direct protein targets (on or off-targets) of a small bioactive molecule. In the YChemH approach, a tagged probe of the molecule of interest is used as a bait to screen for protein targets from one of our 135+ domain-enriched high-complex cDNA libraries prepared from any cell type, tissue or organism.
Thanks to our complete solution, you'll be able to optimize the success rate of your drug discovery program.

Our solutions

ULTIMATE YChemH Principle

ULTIMATE YChemH Principle
Our ULTImate Libraries
ULTImate YChemH key Benefits
Deliverables
Interactions validation
+

The Yeast Three-Hybrid relies on the reconstitution of a functional transcription factor (TF) followed by the expression of a reporter gene in genetically modified yeast cells. Upon a drug–target protein interaction, the DNA Binding Domain (DBD) of the TF is brought in close proximity to its Activation Domain (AD). This activates the transcription of the HIS3 reporter gene, allowing yeast cells to grow on selective medium lacking histidine. The DNA of positive clones are sequenced to reveal the interacting partners.


The YChemH technology is a three-component system

  • A hook protein fused with a DBD
  • A target protein library fragment fused to the transcriptional AD
  • A small molecule tagged with a ligand that binds to the hook protein
+

We offer a large collection of cDNA and genomic libraries (135+) to accommodate your target identification screening project. The libaries are constructed from tissues, cell lines, primary cells or whole organisms derived from various species including human, rodents, plants, bacteria, etc. Using a patent cell-to-cell mating assay, libraries are screened to saturation, averaging an 8-fold in library coverage.
New libraries are constructed upon request.

+
  • Identification of direct protein targets
  • Reduced drug efflux due to the creation of a proprietary mutant yeast strain
  • Exhaustive and unbiased whole proteome screening approach
  • Uncovers multiple targets in a single screen, but only one at a time.
  • Highly sensitive transcriptional readout - Detection of weak and rare interactions
  • No competition with abundant or strong interacting partners; no washing steps
  • Technically simplistic method: Yeast used as a screening tool; no mass spectrometry equipment
  • Integrated bioinformatics: Includes assigning confidence scores & mapping of the interacting domains
  • Flagged false positives
  • Quick turnaround

The results of your ULTImate YChemH screen are summarized with three complementary user-friendly deliverables:

  • A Results summary with the identified protein partners, the detailed fragments and our confidence score - Predicted Biological Score, PBS®.
  • An Excel® raw data table with the sequences and the Genbank accession number
  • The ‘DomSight’ contains a graphical comparison of the experimental interacting domain for each partner and the SID®, with known functional and structural domains
    Our scientific project leaders support the interpretations of your results and help you to focus on the most relevant interactions for the best outcome of your project.

The following in-yeast validation experiments can be performed after a YChemH screen:

  • 1-by-1 in cell validation assays with selected protein targets identified in the YChemH screen (include negative controls) to confirm binding and check specificity
  • Competition experiments using a defined concentration of chemical probe, the desired protein target and in the presence of increasing concentrations of "free" active or inactive compound
  • Interaction Domain Mapping experiments (IDM) in order to better define the interaction domain

our publications

Customer Publications

PAPD5/7 Are Host Factors That Are Required for Hepatitis B Virus RNA Stabilization.

Mueller H, Lopez A, Tropberger P, Wildum S, Schmaler J, Pedersen L, Han X, Wang Y, Ottosen S, Yang S, Young JAT, Javanbakht H. Hepatology. 2019 Apr;69(4):1398-1411. doi: 10.1002/hep.30329. Epub 2019 Mar 1. PMID: 30365161.

A fishing expedition for antidiabetic drugs : identifying new avenues to stimulate beta-cell regeneration

Karampelias, C., Thesis, Karolinska Institutet, 2021.

Chemical Dimerizers in Three-Hybrid Systems for Small Molecule-Target Protein Profiling

De Clercq DJ, Tavernier J, Lievens S, Van Calenbergh S. ACS Chem Biol. 2016 Aug 19;11(8):2075-90. doi: 10.1021/acschembio.5b00811. Epub 2016 Jun 20. PMID: 27267544.

FAQ

Do you have a question?

Would you like to discuss your project?