Marquette University

Triad Therapeutics, Inc.

Triad Liquidating Company, LLC

Concordia University

Traid Therapeutics, Inc.

Daniel S Sem

Maurizio Pellecchia

Anna Maria Tempczyk-Russell

Min Sang Lee

Mark Kelly

Qing Dong

Jianqiang Wang

Phani Kumar Pullela

William A Donaldson

Yong Qin

Terrence S Neumann

Hugo Villar

Disclosed are substituted (4'-hydroxylphenyl)cycloalkane compounds and there use as selective agonists of the estrogen receptor beta isoform (ER&#x3b2;). The disclosed compounds may be formulated as pharmaceutical compositions and administered to treat diseases associated with ER activity, such as proliferative diseases and disorders and/or psychiatric diseases or disorders.

Substituted (4'-hydroxyphenyl)cyclohexane compounds and uses thereof as selective agonists of the estrogen receptor beta isoform

Disclosed are dithio compounds that include a quenched fluorophore and a non-fluorophore peptide linked via a dithio bond to the fluorophore. The dithio compounds may be used in methods for detecting thiol-containing compounds or dithio-containing compounds. The dithio compounds also may be used as cellular probes where the peptide portion of the compounds targets the compounds to a specific cellular location.

Methods for detecting dithio-containing proteins using quenched fluorophores conjugated to peptides via linkers containing dithio groups

The invention provides a method for identifying a ligand that binds to a macromolecular target. The methods involve (a) attaching an antenna moiety to a first ligand, wherein the ligand binds specifically to a macromolecular target; (b) providing a sample comprising the macromolecular target, the first ligand and a candidate second ligand under conditions wherein the first ligand and the macromolecular target form a bound complex; (c) detecting a subset of magnetization transfer signals between the antenna moiety of the first ligand and the second candidate ligand, wherein the signals are obtained from an isotope edited NOESY spectrum of the sample; thereby determining that the two ligands are proximal in a bound complex, and identifying a second ligand that binds to the macromolecular target.

Nuclear magnetic resonance assembly of chemical entities using advanced antenna probes

Disclosed herein are dithio compounds that include at least one fluorophore. The compounds additionally may include a different fluorophore or a non-fluorophore. The dithio compounds may be used as reagents for detecting thiol-containing compounds.

Dithio compounds

Disclosed are methods for detecting thiol-containing nucleotide diphosphates. The methods utilize thiol-reactive fluorescent reagents.

Methods for detecting thiol-containing nucleotide diphosphates with thiol-reactive fluorescent reagents

The invention provides a method for obtaining a binding compound for a protein family, wherein the members of the protein family bind a common ligand. The method includes the steps of (a) providing a sample containing a protein from the protein family, a first ligand and a second ligand under conditions wherein the first ligand, the second ligand and the protein form a bound complex; (b) detecting magnetization transfer between the first ligand and the second ligand in the bound complex, thereby determining that the two ligands are proximal in the bound complex; and (c) obtaining a candidate binding compound including the first ligand, or a fragment thereof linked to the second ligand, or a homolog thereof, whereby the population contains binding compounds that bind to members of the protein family.

Nuclear magnetic resonance assembly of chemical entities

Disclosed are assays useful for detecting kinase activity. The assays utilize thiol-reactive fluorescent reagents and include reacting a reaction mixture that contains an ATP analog such as ATP&#x3b2;S to form an ADP analog such as ADP&#x3b2;S if kinase activity is present in the reaction mixture. The ADP analog reacts with the thiol-reactive fluorescent reagent and the reagent exhibits a change in fluorescence, thereby indicating that kinase activity is present in the reaction mixture.

Method for detecting kinase activity with thiol reactive fluorescent reagents

Methods for rapidly identifying drug candidates that can bind to an enzyme at both a common ligand site and a specificity ligand site, resulting in high affinity binding. The bi-ligand drug candidates are screened from a focused combinatorial library where the specific points of variation on a core structure are optimized. The optimal points of variation are identified by which atoms of a ligand bound to the common ligand site are identified to be proximal to the specificity ligand site. As a result, the atoms proximal to the specificity ligand site can then be used as a point for variation to generate a focused combinatorial library of high affinity drug candidates that can bind to both the common ligand site and the specificity ligand site. Different candidates in the library can then have high affinity for many related enzymes sharing a similar common ligand site.

NMR-solve method for rapid identification of bi-ligand drug candidates

A method for preferentially observing an exposed position () of a macromolecule. A sample is obtained having a macromolecule () with a first proton () and a second molecule () with a second proton (); then applying a magnetic field () to the sample and irradiating the sample with a pulse sequence () that preferentially demagnetizes protons of the macromolecule () relative to the second proton (); allowing the second proton () to exchange () with an exposed proton () of the macromolecule; and detecting the magnetization from the relatively magnetized second proton (), which is now bound to the exposed position () of the macromolecule. The invention also provides a method for observing a position in the macromolecule that bind a ligand.

SEA-TROSY and related methods

Methods for rapidly identifying drug candidates that can bind to an enzyme at both a common ligand site and a specificity ligand site, resulting in high affinity binding. The bi-ligand drug candidates are screened from a focused combinatorial library where the specific points of variation on a core structure are optimized. The optimal points of variation are identified by which atoms of a ligand bound to the common ligand site are identified to be proximal to the specificity ligand site. As a result the atoms proximal to the specificity ligand site can then be us ed as a point for variation to generate a focused combinatorial library of high affinity drug candidates that can bind to both the common ligand site and the specificity ligand site. Different candidates in the library can then have high affinity for many related enzymes sharing a similar common ligand site.

Growing community of inventors

New Berlin, WI, United States of America

Daniel S Sem