The Yeast-2-Hybrid profiling system

Phenex has cloned a comprehensive list of human Nuclear Receptors Ligand Binding Domains (LBDs) and a huge panel of Cofactors (CoF) that are described in the literature. This panel is used by Phenex to determine ligand-dependent Cofactor recruitment in the yeast system. For this purpose, Phenex employs the direct mating of respective NR and CoF interaction vectors harboured by a yeast a and alpha type, respectively. Together with an robotized all-fluid phase dilution scheme, Phenex is able to assay for ligand dependency of Cofactor interactions in a dose response manner.

The Yeast-2-Hybrid direct mating system is ideal to obtain an overview which Cofactor (constructs) are recruited to a certain Nuclear Receptor in a ligand-dependent fashion. Each NR has its own distinct CoF binding pattern upon administration of its cognate native ligand. However, subtle differences between classical full agonists and partial agonists can be detected in this system. This makes it a good starting point to analyze SNuRM-effects of a set of NR binding drug candidates.

The yeast system is a powerful tool for the comparative analysis of ligand induced Cofactor recruitment patterns!

Application examples for the Yeast-2-Hybrid system:

- NRs have their specific cofactor profile
- Compound selective cofactor recruitment by the ERα
- Compound selective PPARγ-LBD cofactor recruitment
- Identifying selective compounds for the Liver X Receptor (LXR)