Five novel hit-finding compound libraries are aimed at voltage-dependent and ligand-gated channels, two of the most important and commonly chosen classes of ion channels for drug discovery
Five novel hit-finding compound libraries targeting the ion channel gene family have been released by BioFocus DPI.
The three new SoftFocus Ion Channel (SFI) libraries target voltage-dependent channels, primarily focusing on sodium and calcium channels to complement BioFocus DPI's earlier libraries focused on potassium channels.
These libraries were designed using BioFocus DPI's proprietary chemogenomic tool, helical domain recognition analysis.
The two new FieldFocus libraries target members of the transient receptor potential (TRP) channel, including TPRV, TRPM and TRPAs, and were created in collaboration with Cresset BioMolecular's FieldPrint technology.
The compounds within these five new ion channel libraries have attractive physicochemical properties, making them ideal starting points in hit-to-lead programmes.
Furthermore, robust synthetic procedures have been developed, which will help facilitate rapid hit follow-up.
The libraries are part of BioFocus DPI's commitment to provide an unparalleled service offering in ion channel drug discovery including, in-house state-of-the-art high-throughput ion channel screening.
"Our entire design and synthesis process is driven by the fundamental belief that drug discovery will be more successful by starting with novel molecules designed to selectively interact with distinct gene families," said Phil Dudfield, VP discovery products, BioFocus DPI.
"This approach results in the outstanding success that our compound libraries have delivered for our partners' drug discovery programmes".
SFI libraries are created using BioFocus DPI's proprietary helical domain recognition analysis (HDRA) chemogenomic tool.
HDRA links X-ray, sequence alignment and SAR data and is used to rationalise scaffold binding in the pore region of ion channels and to guide monomer selection.
This design method has proved remarkably successful with the first generation of SoftFocus ion channel libraries (SFI01-04) delivering potent and selective compound series against a variety of ion channel drug targets.
FieldFocus is a ligand-centred approach to library design based around molecular fields and is used to target ligand gated ion channels.
Cresset's proprietary FieldPrint technology allows the accurate description of molecules in terms of their surface properties or 'fields'.
Initial feedback from screening of the first FieldFocus library (FFI01) has shown the effectiveness of this approach, says Biofocus DPI.
