BioWorld International Correspondent
LONDON - Cresset BioMolecular Discovery Ltd. launched FieldScreen for in silico drug discovery. The product is based on analyzing the molecular fields on the surface of a target, rather than its molecular structure.
The technology draws on the fact that two structurally different drug molecules can bind to the same region of a protein and have the same therapeutic effect, if they have similar molecular fields.
That's not a new observation, but Cresset claims to be the first company to characterize molecular fields using its Extended Electron Distribution approach to provide a structure-independent method of aligning actives from different chemical classes. Using FieldScreen it is possible to search compound libraries to select compounds with diverse structures but the same biological function.
Cresset has determined the molecular fields, or FieldPrint, of 1.5 million commercially available compounds. They can be matched against the FieldPrint of an existing lead to find new series of compounds with similar fields and biological activity but diverse structures.
For example, Cresset said it has replaced peptides with non-peptides, and steroids with non-steroid leads.
Sally Rose, director of business development at Letchworth-based Cresset, told BioWorld International, "FieldScreen can be used for any target, but it is particularly appropriate if there isn't a crystal structure, or for hard-to-crystallize structures."
Most of the company's work to date has been carried out on G protein-coupled receptors. "[FieldScreen] is very useful if there is a lot of movement in the crystal, where you can have different crystal structures depending on which ligand is bound," she said.
Rose said the technology is complementary to structure-based drug design. "If I had a crystal structure that would probably be my first port of call. But FieldScreen can identify important interactions," she said.
In general, FieldScreen provides a higher hit rate. "In some cases there is an exceptional hit rate - we have got up to 35 percent," Rose said. "This compares to high-throughput screening, where you expect 0.1 percent, or docking, where if you have a good algorithm you can expect a single-digit hit rate."
To date, Cresset has provided the technology on a fee-for-service basis, but FieldScreen has been launched to meet demand from customers to take the system in-house. The first system has been installed at an unnamed biotechnology company.
Cresset began in November 2001 with £780,000 (US$1.5 million) from the Wellcome Trust to develop the software. It is now looking for £300,000 to develop other applications of the system and to partner with companies with targets on joint discovery programs.