peakexplorer™ - GPCR

It is estimated that over 50% of marketed drugs act on G-Protein Coupled Receptors (GPCRs).The peakexplorer™ GPCR library of screening compounds has been designed specifically to address gaps in commercially available compound collections and to provide greater diversity in drug discovery.

The library was created through a novel process that combined in silico pharmacophore modelling, design and virtual screening algorithms developed by our strategic partner, De NovoPharmaceuticals. For a given set of known GPCR antagonists, pharmacophore modelling optimises molecular similarity with respect to those features known to be important in GPCR binding as a function of ligand conformation, ionisation state and tautomeric state. This process resulted in a binding site model that defined both the volume and key site points and was used as input for the de novo design of novel ligands.

Fragment based structure design was used to assemble molecular fragments, derived from known GPCR ligands and proprietary Peakdale chemistries, within the confines of the binding site model. Physico-chemical properties such as hydrogen-bonding, lipophilicity, electrostatic and steric parameters were integrated during this virtual synthesis. The resulting designs were evaluated and optimised by Peakdale’s medicinal chemists to define suitable chemotypes.

Peakdale’s chemists then introduced a range of decorations using both commercially available and proprietary monomers onto these chemotypes to create a virtual library of molecules with lead-like properties. The virtual compounds were then docked into the pharmacophore model and ranked to generate a set of molecules that show best fit to the GPCR binding site.

The result is a library containing over 6,500 compounds based around 34 major chemotypes, synthesised to the highest standard by Peakdale’s chemists. The molecules are characterised for purity by HPLC (minimum 85%) and for structure by LC-MS and/or ¹H NMR, before being formatted into standard or customer-supplied vials and plates, as powder or solution.

Design of the Library (154kb)

Information on Chemotypes (212kb)

Library Data (225kb)

Order the Library CD-ROM