Glaxosmithkline LLC

Dewpoint Therapeutics, Inc.

Praecis Pharmaceuticals, Inc.

Ensemble Therapeutics Corporation

Stephen Paul Hale

Malcolm L Gefter

Barry A Morgan

Richard W Wagner

Dennis R Benjamin

Christopher C Arico-Muendel

David I Israel

Malcolm J Kavarana

Matthew Clark

Nils Jakob Vest Hansen

Raksha A Acharya

George J Franklin

Paolo A Centrella

Mark Andrew Murcko

Bruce Aaron Beutel

Steffen Phillip Creaser

Benjamin A Seigal

Nicholas K Terrett

Peter Jeffrey Dandliker

Edgar Erik Boczek

Matthäus Mittasch

Frank G Favaloro, Jr

Timothy F Briggs

Diana Maria Mitrea

Alexander Szewczak

Ina Poser

Steffan Phillip Creaser

Nils Jakob Hansen

Atli Thorarensen

Li Huang Xing

Jinbo Lee

Julian F Bond

Kelley C Shortsleeves

Daniel Wang

Wei-Chuan Sun

William H Connors

Cheri Snedeker

Paulo A Centrella

Tyler J Cipriani

Dingxue Yan

Sethu L Alexander

Michael Taylor

Mathew A Clark

Methods of identifying a compound, such as a test compound, and applications thereof are provided. For example, methods of identifying a compound that preferentially affects, increases, or decreases a level of association of a macromolecule with one or more target condensates or methods of identifying a compound that preferentially causes a macromolecule to associate or disassociate with one or more target condensates are provided. Additionally, methods of designing and/or identifying and/or making a compound, or portion thereof, with a desired characteristic are provided.

Methods of screening for condensate-associated specificity and uses thereof

Methods of assessing, such as characterizing or determining, condensate-associated characteristics of a compound, such as a test compound, and applications thereof are provided. For example, methods of determining a partition characteristic of a test compound in a target condensate, methods of determining a relative partition characteristic of a test compound in a target condensate, and methods of determining a condensate preference profile of a test compound are provided. Additionally, methods of designing and/or identifying and/or making a compound, or portion thereof, with a desired relative condensate partition characteristic are provided.

Methods of characterizing condensate-associated characteristics of compounds and uses thereof

The invention relates generally to macrocyclic compounds of formula I and their therapeutic use. More particularly, the invention relates to macrocyclic compounds that modulate the activity of IL-17 and/or are useful in the treatment of medical conditions, such as inflammatory diseases and other IL-17-associated disorders. 

Macrocyclic compounds for modulating IL-17

The present invention provides a method of synthesizing libraries of molecules which include an encoding oligonucleotide tag.

Methods for synthesis of encoded libraries

Disclosed herein are macrocyclic compounds and methods for their synthesis and use. In particular, macrocyclic compounds are disclosed that modulate the activity of tumor necrosis factor alpha and/or are useful in the treatment of medical conditions, such as, rheumatoid arthritis, psoriasis, and asthma.

Macrocyclic compounds for inhibition of tumor necrosis factor alpha

The present invention provides a method for identifying a compound of interest by screening libraries of molecules which include an encoding oligonucleotide tag.

Methods for identifying compounds of interest using encoded libraries

The present invention provides methods of synthesizing a molecule comprising a functional moiety which is operatively linked to an encoding oligonucleotide. The methods include providing an initiator compound comprising an initial functional moiety comprising n building blocks, wherein the initial functional moiety comprises at least one reactive group, and is operatively linked to an initial oligonucleotide; reacting the initiator compound with a building block comprising at least one complementary reactive group, under conditions suitable for reaction of the complementary reactive group to form a covalent bond; and reacting the initial oligonucleotide with an incoming oligonucleotide corresponding to the building block in the presence of an enzyme which catalyzes ligation of the initial oligonucleotide and the incoming oligonucleotide, under conditions suitable for ligation of the incoming oligonucleotide and the initial oligonucleotide to form an encoding oligonucleotide.

The present invention provides methods of synthesizing libraries of molecules comprising a functional moiety which is operatively linked to an encoding oligonucleotide, wherein the encoding oligonucleotide comprises a capping sequence containing degenerate nucleotides. The methods generally include providing a solution comprising initiator compounds comprising an initial functional moiety comprising n building blocks which is operatively linked to an initial oligonucleotide; dividing the solution into reaction vessels; reacting the initiator compounds in each reaction vessel with a building block comprising a complementary reactive group to form a covalent bond; and reacting the initial oligonucleotide in each aliquot with a distinct incoming oligonucleotide in the presence of an enzyme which catalyzes the ligation of the incoming oligonucleotide and the initial oligonucleotide, under conditions suitable for enzymatic ligation of the incoming oligonucleotide and the initial oligonucleotide to form an encoding oligonucleotide.

The present invention provides methods of synthesizing libraries of molecules comprising a functional moiety which is operatively linked to an encoding oligonucleotide. The methods generally include providing a solution comprising initiator compounds comprising an initial functional moiety which comprises n building blocks which comprise at least one reactive group, which is operatively linked to an initial oligonucleotide; dividing the solution into reaction vessels; reacting the initiator compounds in each reaction vessel with a building block comprising a complementary reactive group to form a covalent bond; and reacting the initial oligonucleotide in each aliquot with a distinct incoming oligonucleotide in the presence of an enzyme which catalyzes the ligation of the incoming oligonucleotide and the initial oligonucleotide, under conditions suitable for enzymatic ligation of the incoming oligonucleotide and the initial oligonucleotide to form an encoding oligonucleotide which identifies the structure of the functional moiety.

Growing community of inventors

Belmont, MA, United States of America

Stephen Paul Hale