DiscoverRx develops, commercializes and manufactures reagents and assay kits for the drug discovery market. Their focus is on lucrative protein target classes, such as G-protein-coupled receptors and kinases.The company is built around a proprietary technology called enzyme fragment complementation or EFC which forms the basis of the assays that they design and market. In EFC, two β-galactosidase fragments are employed which are themselves inactive. One fragment has an inactivating deletion while the second fragment has a complementing fragment; in solution where both EA and ED are present, certain pairs of fragments combine spontaneously to form active complexes. Some pairs of fragments interact only weakly and combine to produce enzyme activity only when forced into close proximity by virtue of their attachment to proteins which bind to each other. This property permits evaluation of intracellular protein interactions for use in high throughput screening of drug candidates for their effect on specific cellular pathways. The company offers a wide variety of cell lines that produce such fusion products. Wikipedia.
Treiber D.K.,DiscoveRX |
Shah N.P.,University of California at San Francisco
Chemistry and Biology | Year: 2013
In this issue of Chemistry & Biology, Hari and colleagues show that two positions in kinase active sites, including the well-known " gatekeeper" residue, regulate "in" versus "out" conformations of the conserved "DFG" motif. These findings suggest yet another role for the gatekeeper residue. © 2013 Elsevier Ltd. All rights reserved. Source
Berg E.L.,DiscoveRX |
Hsu Y.-C.,Eli Lilly and Company |
Lee J.A.,Eli Lilly and Company
Advanced Drug Delivery Reviews | Year: 2014
There is renewed interest in phenotypic approaches to drug discovery, using cell-based assays to select new drugs, with the goal of improving pharmaceutical success. Assays that are more predictive of human biology can help researchers achieve this goal. Primary cells are more physiologically relevant to human biology and advances are being made in methods to expand the available cell types and improve the potential clinical translation of these assays through the use of co-cultures or three-dimensional (3D) technologies. Of particular interest are assays that may be suitable for industrial scale drug discovery. Here we review the use of primary human cells and co-cultures in drug discovery and describe the characteristics of co-culture models for inflammation biology (BioMAP systems), neo-vascularization and tumor microenvironments. Finally we briefly describe technical trends that may enable and impact the development of physiologically relevant co-culture assays in the near future. © 2014 Elsevier B.V. Source
DiscoveRX | Date: 2013-10-21
Methods and materials are disclosed for use in an enzyme fragment complementation assay using complementary fragments of -galactosidase to study the trafficking of proteins in a cell. Compounds that bind to a target peptide have been found to affect protein folding and therefore trafficking. -Galactosidase fragments, an enzyme donor (ED) and an enzyme acceptor (EA), are fused to a target peptide and to an intracellular compartment protein, wherein the compartment is involved in intracellular trafficking. Contacting the cell with a compound that binds to the target peptide results in enhanced movement of the protein through the cellular trafficking pathway comprised of the endoplasmic reticulum, Golgi apparatus, the plasma membrane, endosomes, etc. Using this approach, compounds that bind to a target peptide and alter its ability to traffic through the normal cellular pathway can be readily detected.
DiscoveRX | Date: 2015-07-28
Provided herein are nucleic acid tags that are linked to, or capable of linking to, a protein of interest. In particular, the nucleic acid tags are oligonucleotides comprising a reporter function and a protein tagging function. Also provided herein, are nucleic acid tag compositions, kits and methods of use thereof.
DiscoveRX | Date: 2013-02-05
Methods and compositions are provided to measure the binding of a test compound to a target peptide by measuring the effect of the compound on the abundance of the target peptide inside a cell. The target peptide may bind the test compound at an active site or an allosteric site, and it has been found that such binding may stabilize the target peptide against cellular degradation. The target peptide will preferably comprise a destabilizing mutation which shortens the half life of the target peptide within the cell, typically a mammalian cell. Test compounds, including small molecules, have been found to stabilize target peptides. Also provided are systems and kits for use in practicing the methods.