Conformetrix Ltd - Key Structures for Molecular Discovery

Conformetrix Ltd is a pre-clinical drug discovery company, providing unique ligand-based approaches for hit identification and lead optimization, rapidly identifying novel chemical scaffolds for drugging any therapeutic target. Conformetrix can solve the dynamic 3D-structure of any organic molecule. This is a world-first capability and delivers key information on new drug chemistry for medicinal and computational chemists.

Established in 2007, Conformetrix are based in the Manchester Incubator Building, part of the specialist business incubation facilities managed by the University of Manchester Incubator Company (UMIC).

Context

Conformetrix exploit the templates provided by Mother Nature herself - the natural ligands for important receptor proteins such as GPCRs and ion-channels. Their platform technology is a set of proprietary analytical tools that accurately determine the preferred 3D-shapes of these natural ligands and the drugs that mimic them. Furthermore, it also quantifies the dynamic range of movement around these preferred 3D-shapes (what Confrometrix term a molecule's 4D-structure).

This information is vital, not only to understanding how drugs work, but also for quickly and efficiently improving new compounds in development.

Conformetrix's technology uses a vast amount of experimental Nuclear Magnetic Resonance (NMR) data, recorded on unlabeled compound (no C13 or N15 isotopic labeling) and without recourse to electrostatics or Van der Waals calculations. Their 4D-structure provides unparalleled insight and guidance for processes such as virtual screening, lead optimisation, QSAR and scaffold-hopping.

Services

- Virtual Screening

Compared to purely theoretically derived 3D-structures, an experimentally determined Conformetrix Gold-level structure is far more likely to provide high-value virtual hits. It is also likely to be more accurate than a reverse-engineered pharmacophore map derived from a co-crystal of the protein-bound ligand.

- Hit Characterisation

It is often extremely difficult to identify common pharmacophore motifs amongst groups of unrelated hit chemistries, irrespective of whether they've been selected in silico or in vitro. Conformetrix Bronze-level structures provide a means of quickly and simply getting to this key information.

- Lead Optimisation / QSAR

A Silver-level structure provides sufficient resolution to quantify the preferred 3D-structures of lead series, helping rationalise what might otherwise be inexplicable QSAR data. It can also help guide optimisation strategies, particularly when overlaid on a 4D-template structure of the natural ligand. We can highlight areas of deviation or identify where to add functional groups to provide a better match.

- Drugging GPCRs & Ion-Channels and Other Intractable Therapeutic Targets

Conformetrix technology finally offers a viable alternative to structure-based approaches to discovery. A Gold-level structure of the natural ligand for any protein target provides a sufficiently accurate 3D-blueprint for designing NCEs and can be obtained in a fraction of the time of crystallographic data.

- IP Protection / Competitor Drug Analysis

Information provided by Conformetrix Gold-level structures is uniquely powerful for informing IP protection strategies, determining where modifications can usefully be made and helping medicinal chemists to focus on those derivatives likely to be of most value.

Conformetrix is currently working with a number of leading drug development companies, using its unique ligand-based approach to discovery to speed pre-clinical development. Company representatives have attended and presented at recent conferences including BIO in Atlanta May 2009 and OpenEye’s Annual European Molecular Modeling Meeting EuroCup III meeting in Toledo, Spain in April 2009.

Contact

Gordon Barker, Commercial Director

Conformetrix Ltd.

Core Technology Facility

46 Grafton Street, Manchester, M13 9NT.

+ 44(0) 161 606 7203        http://www.conformetrix.com/