Ambit Biosciences Corporation

Discoverx Corporation

Eurofins Discoverx Corporation

Daniel Kelly Treiber

Pietro Ciceri

David J Lockhart

Patrick Parvis Zarrinkar

Lisa Wodicka

Elena Menichelli

Jean-Michel A Lelias

Mike Morrison

Jeremy Hunt

Hitesh K Patel

Zdravko V Milanov

Shamal Anil Mehta

Warren G Lewis

William H Biggs, Iii

Miles A Fabian

Ksenya Cohen Katsenelson

Jean-Michael A Lelias

Lisa M Wodicka

The present disclosure provides a compound screening method comprising screening a test compound that binds a target protein of interest and another ligand protein that is not previously known to form a complex, comprising, (i) in the presence and absence of a test compound, incubating an immobilized ligand protein with a target protein of interest, comprising a nucleic acid tag, wherein the protein of interest and the nucleic acid tag differ from each other; (ii) removing unbound target protein of interest; and (iii) detecting the presence or absence of complex between the immobilized ligand protein, test compound, and the target protein of interest, wherein an increase in the amount of target protein of interest bound to the immobilized ligand protein in the presence of test compound as compared to the absence of test compound indicates the test compound binds to and enables protein-protein complex formation between the immobilized ligand protein and the target protein of interest.

Molecular glue screening assays and methods for practicing same

Disclosed are methods for detecting and quantitatively measuring a binding property of a compound to a target macromolecule, wherein the target macromolecule is subject to denaturation and is linked to a labeling peptide, such as a short enzyme fragment. The method uses a fluid mixture comprising (i) a chimeric molecule comprising a target macromolecule linked to the labeling peptide, wherein the target macromolecule may be a chimeric protein expressed by and within an intact viable cell and (ii) a compound being measured for binding to the target macromolecule, wherein said target macromolecule is subject to denaturation. After allowing for binding of the compound (e.g. a small molecule inhibitor of the target macromolecule), one detects a signal from the labeling peptide, such as by enzyme fragment complementation. This signal indicates a differential between denatured and non-denatured target macromolecules and thereby indicates a differential between target macromolecules not bound to the compound and target macromolecules bound to the compound, respectively.

Methods for measuring binding and cellular engagement of ligands with target proteins

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.

Detectable nucleic acid tag

Disclosed are methods for detecting and quantitatively measuring a binding property of a compound to a target macromolecule, wherein the target macromolecule is subject to denaturation and is linked to a labeling peptide, such as a short enzyme fragment. The method uses a fluid mixture comprising (i) a chimeric molecule comprising a target macromolecule linked to the labeling peptide and (ii) a compound being measured for binding to the target macromolecule, wherein said target macromolecule is subject to denaturation. After allowing for binding of the compound (e.g. a small molecule inhibitor of the target macromolecule), one detects a signal from the labeling peptide, such as by enzyme fragment complementation. This signal indicates a differential between denatured and non-denatured target macromolecules and thereby indicates a differential between target macromolecules not bound to the compound and target macromolecules bound to the compound, respectively.

Homogenous thermal shift ligand binding assay

The invention provides methods for determining the interactions between phage-displayed proteins and test molecules. The phage-displayed proteins are contacted with a reference moiety in the presence and absence of a test molecule; the behavior of the phage-displayed proteins as a function of concentration of the test molecule permits calculation of the binding affinity of the phage-displayed protein for the test molecule.

Assays and kits for detecting protein binding

Provided herein are assays useful, for example, for determining the activity of a protein involved in a cellular process. In some embodiments, the activity of the protein is assessed using a nucleic acid tag, and in particular, by detecting the presence of a nucleic acid tag. Such assays can be used, for example, to study the effects of test compounds as modulators, e.g., inhibitors, agonists and antagonists, of protein activity.

Cellular assay employing detectable protein

The present invention provides an advance in phage display technology by permitting the uncoupling of the propagation of phages containing inserted sequences encoding heterologous polypeptides from the expression of said polypeptides. The invention provides phage constructs and methods for their use to permit phage coat protein expression, and thus phage propagation, in the absence of display of heterologous polypeptides, which may be expressed as a fusion with said coat protein in a regulated manner.

Uncoupling of DNA insert propagation and expression of protein for phage display

The invention provides pyrrole-containing compounds and methods of use thereof. Kits and pharmaceutical compositions comprising the pyrrole compounds of the invention are also provided. The compounds and compositions disclosed herein are preferably used in the treatment of neurodegenerative diseases, cardiovascular diseases, proliferative diseases, and visual disorders. In particular, methods and compositions for the treatment of stroke are disclosed herein.

Growing community of inventors

San Diego, CA, United States of America

Daniel Kelly Treiber