The Protein Interactions Expert



Our Drug Target Identification service: ULTImate YChemH

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Find out more about your small molecule effects and mechanism of action thanks to our drug target identification service: ULTImate Yeast Chemical Hybrid (YchemH).

Thanks to our complete solution, you won't waste your money on the wrong candidate molecule and you'll be able to optimize the success rate of your drug development program and drug profiling project. ULTImate YchemH is based on a compound profiling technique adapted from our ULTImate Y2H™ technology to identify the protein partners of a given bioactive small molecule.

Applications of ULTImate YChemH to your drug profiling project

  • Identify hit targets and decipher drug mechanisms of action following a phenotypic screening (drug profiling, target deconvolution)
  • Study the off-target effects of an active compound
  • Support drug repositioning in new therapeutic areas
  • Evaluate safety of chemicals (toxico-proteomics)

Molecules Tested

  • Small bioactive molecules
  • Drugs under development or marketed

How does this drug target identification service work?

ULTImate YChemH is a direct drug target identification method based on the established yeast two-hybrid (Y2H) technique. The small molecule of interest is used as a bait to screen highly complex protein domain libraries. The small molecule - protein interactions are detected thanks to the reconstitution of an active transcription factor from DNA Binding Domain (DBD) and Activation Domain (AD) moieties.

Three components are used:

  • A hybrid protein containing a DBD fused to an Anchor Binding Protein (ABP)
  • A hybrid protein containing a transcriptional AD fused to a ‘prey’ protein fragment from the library
  • A bait derivative (Anchor – Linker – Small Molecule Bait).

When a "small molecule – prey protein" interaction takes place, the bait derivative bridges the gap between the DBD and the AD thanks to the anchor-ABD interaction. This enables the expression of the reporter gene and subsequent yeast growth on a selective medium. Positive clones are then analyzed by sequencing to identify the protein partners.

More details on this technology can be found on our resource center.

For more information on our screening technology and libraries, please refer to our ULTImate Y2H and ULTImate Libraries pages.

ULTImate YChemH diagram

Formula of a Hybrid Small Molecule

Key-benefits for drug profiling and drug discovery

  • Enhanced drug intake thanks to proprietary permeable yeast strain
  • Exhaustive screening of highly complex protein fragment libraries
  • Multi-anchor and multi-linker approach to optimize the accessibility of the bait molecule
  • Detection of even weak small molecule–protein interactions for in depth compound profiling
  • Full sophisticated bioinformatics analysis of the results including confidence scores
  • Flexible and time-saving target identification service

Deliverables

The results of your ULTImate YChemH screen come fully analyzed to help you focus on the most relevant interactions. The deliverables include the list of identified protein partners, the experimental interaction domain on each protein and a confidence score.

Application Examples

Chidley et al., Nature Chemical Biology (2011)

Shepard et al., ACS Chemical Biology (2013)

 

For any question on this drug discovery service, contact us.

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