Biofocus enters new class of compound libraries
collection of novel low molecular weight compounds. The compilation
will allow drug researchers to find ligands that bind to proteins
without having to invest in specialised structural biology assay
techniques.
The pre-clinical specialists introduce its ThemePair libraries, which aim to bridge the gap between screening small molecular weight ligands ("fragments") and the screening of higher molecular weight compounds
Fragments require structure-based assays to show affinity at millimolar concentrations in contrast to higher molecular weight compounds, which require large numbers of such compounds to be screened at low micromolar concentrations to find hits.
Low molecular weight compounds created using the new paired monomer approach (ThemePair) can be screened for activity using standard bioassays at high concentrations. This is possible due to a focus on the solubility of the novel, low molecular weight ThemePair compounds.
A spokesman for BioFocus told DrugResearcher.com: "There is enormous interest in the pharmaceutical industry in obtaining lead-like compounds for screening which offer the potential to be developed into lead series."
"The compounds in the Themepair libraries fit the expected criteria of low molecular weight and clog. This we see as a real gap in the market."
Each of the 10 different scaffolds in the 500-member ThemePair library has been involved in one position with either an amine or aryl group. These substituents have been chosen to enable the exploration of a range of characteristics, including: steric; electronic factors and the ability to form H-bonds.
However, the substituents have been chosen to generate only low molecular weight products (mostly less than 300 daltons) which assists in producing compounds with solubility and thus having a better chance of being screened at high concentrations.
During library validation, a subset of the library has been proven to have good measured solubility. Furthermore, as they are novel, active compounds possess potential for elaboration into more potent candidate compounds.
"We have developed this approach to ligand discovery in order to allow drug researchers to strike a balance between fragments, which typically need X-ray crystallography or NMR-based screening, and conventional libraries, which comprise a large number of compounds to screen," said Phil Dudfield, director of Discovery Products, at BioFocus.
"This concept creates a new entry point into ligand binding studies," he added.
The first library of approximately 500 compounds will be available for delivery at the end of September 2005. Pricing will be competitive and available to clients upon request
Biofocus' product is in contrast to alternative strategies currently available. They use a fragment-based approach with either X-ray crystallography or NMR as the screening vehicle. The Themepair libraries can be used in conventional biological screens.
BioFocus plans to continue to develop new products under its ThemePair brand to give a range of novel low molecular weight libraries suitable for investigating a range of targets and generating new IPR for customers.
The spokesman added: "We see this as a market growth area as companies look for complementary products to focused libraries and the fragment screening approach."
"It's difficult to predict the level of growth at the moment."
