Targeted Identification

Targeted Identification

Author: ChemViews

Gisbert Schneider and co-workers, Goethe-University, Frankfurt, Germany, report on target profile prediction to identify cross-activities of peroxisome proliferator-activated receptor (PPAR) and farnesoid X receptor (FXR).

PPARs were identified in the 1990s and have become most prominent targets for treatment of metabolic disorders like dyslipidemia and type 2 diabetes mellitus.

It has now been demonstrated that pharmacophore-based similarity searching may be used to predict the target profile of related bioactive compounds.

For one target, FXR, the correctness of the prediction was experimentally confirmed in a cell-based functional assay.

Figure 1. Pseudoreceptor model of compound 1 (gray) aligned with potent and subtype-selective opioid receptor agonists 3 (: IC50 = 0.87 nM; orange) and 4 (: IC50 = 0.7 nM; magenta). Potential receptor interaction sites are shown as colored spheres (green: aromatic, blue: hydrogen-bond donor). For each compound, one CORINA conformation was generated and a PRPS pseudoreceptor model computed. Only mutual pseudoreceptor sites are shown. Due to the closer resemblance of 1 and 4, it is suggested that 1 might preferably interact with opioid receptor. (C) WILEY-VCH


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