The SNuRM^® Approach

Binding of a small molecule ligand to a Nuclear Receptor results in a conformational change of the receptor. This renders Nuclear Receptors capable of displacing Corepressor and of recruiting Coactivator proteins, ultimately resulting in transcriptional response from certain target genes.

The binding pattern of different Cofactors thereby determines how Nuclear Receptors influence different gene expression networks in different cell types.

Small molecule Nuclear Receptor modulators (SNuRMs) can work by selectively affecting the interactions between Nuclear Receptors and Cofactors, resulting in selective gene regulation.

Phenex has established the SNuRM® Approach, a clear rationale to exploit these selective ligand effects for Nuclear Receptor drug discovery. In using this SNuRM® Approach, Phenex measures the protein interaction and gene regulation capabilities conferred upon a Nuclear Receptor by selective ligands and correlates these properties with desired or unwanted biological effects.

Figure: The SNuRM® Model -
ligand specific modulation of the receptor leads to selective cofactor recruitment, finally leading to selective gene regulation or tissue-specific effects.

Further available information:
- SNuRM® Profiling