Ligand-based drug discovery

Conformetrix can identify the precise spatial orientation of key chemical groups necessary to drug the active site of a target protein directly from the 4D-structure of a known ligand for that target (i.e. in the absence of any protein).

Once a natural ligand for a given target has been identified, we can obtain sufficient structural data to rationally drug that target in less than two months!

An IP 'land-grab'

We are currently solving the 4D-structures of a wide range of natural ligands (e.g. peptide hormones) known to target therapeutically important receptor proteins. This growing database of 4D-structures represents a unique and high-value intellectual property portfolio. It also reveals Mother Nature's own strategies for drugging a wide range of previously intractable targets.

For our in-house discovery programs, we are using these natural-ligand blueprints to rapidly identify and then optimise novel small molecule chemistries for a range of key GPCRs and ion-channels. Click here to learn more about how we do this.

The image below right illustrates just how powerful this ligand-based approach can be. It depicts an overlay of the mode conformers for the natural peptide ligand Ang1-7 (in yellow), with those for the former blockbuster drug Lisinopril (in blue).

The data underlying this image not only explains why this drug works (it mimics the end of the signalling molecule that normally controls blood pressure) but it also explains how to design new and improved ACE inhibitor drugs.

Conformetrix are looking to collaborate with key players in the pharmaceutical industry, with a view to entering into longer-term R&D partnerships, using this new ligand-based approach to discovery for previously intractable disease targets.

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