Glaxosmithkline LLC

X-chem, Inc.

Praecis Pharmaceuticals, Inc.

X-rx, Inc.

Matthew Clark

Richard W Wagner

Malcolm L Gefter

Barry A Morgan

Dennis R Benjamin

David I Israel

Christopher C Arico-Muendel

Malcolm J Kavarana

Stephen Paul Hale

Anthony Dominic Keefe

Raksha A Acharya

Nils Jakob Vest Hansen

George J Franklin

Paolo A Centrella

Ying Victor Zhang

Steffen Phillip Creaser

John William Cuozzo

Ce Wang

Haihong Ni

Alexander Litovchick

Mark J Mulvihill

Diana Gikunju

Heather Thomson

Frank Ruebsam

Louis Renzetti

Lee Babiss

Steffan Phillip Creaser

Zhifeng Xie

Paulo A Centrella

Christopher D Hupp

Ying Zhang

Anthony D Keefe

John W Cuozzo

Nils Jakob Hansen

John Cuozzo

The present invention relates to complexes of oligonucleotide-encoded libraries and methods of tagging and using such libraries. In particular, the oligonucleotides and methods can include complexes having at least one linkage for which a polymerase has reduced ability to read or translocate through.

DNA-encoded libraries having encoding oligonucleotide linkages not readable by polymerases

The present invention relates to oligonucleotide-encoded libraries and methods of tagging such libraries. In particular, the methods and oligonucleotides can include one or more 2'-substituted nucleotides, such as 2&#x2032;-O-methyl or 2&#x2032;-fluoro nucleotides, and other conditions or reagents to enhance enzyme ligation or one or more chemical functionalities to support chemical ligation.

Methods for tagging DNA-encoded libraries

The present invention relates to compounds according to Formula I and pharmaceutically acceptable salts, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancer, lymphocyte homing, chronic inflammation, neuropathic pain, fibrotic diseases, thrombosis, and cholestatic pruritus, mediated at least in part by ATX. 

Substituted spirocyclic inhibitors of autotaxin

The present invention relates to compounds according to Formula 1 and pharmaceutically acceptable salts, synthesis, intermediates, formulations, and methods of disease treatment therewith, including cancer, lymphocyte homing, chronic inflammation, neuropathic pain, fibrotic diseases, thrombosis, and cholestatic pruritus, mediated at least in part by ATX. 

The present invention features benzhydrol-pyrazole derivatives and related compounds having kinase inhibitory activity. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions, such as cancers, inflammatory disorders, or autoimmune disorders.

Benzhydrol-pyrazole derivatives having kinase inhibitory activity and uses thereof

The present invention features tryptoline derivatives and related compounds having kinase inhibitory activity. The compounds of the invention, alone or in combination with other pharmaceutically active agents, can be used for treating or preventing various medical conditions, such as cancers, inflammatory disorders, or autoimmune disorders.

Tryptoline derivatives having kinase inhibitory activity and uses thereof

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

Methods for synthesis of encoded libraries

The present invention provides, at least in part, compounds of formula (I): or a pharmaceutically acceptable salt thereof, wherein Z, Z, Z, R, x, y, R, R, R, R, R, Rand Rare described herein, as well as methods for their identification, their preparation, pharmaceutical compositions containing them, and their use as Aurora A kinase inhibitors in treatment, e.g., of cancer and other proliferative disorders. 

Aurora kinase inhibitors from an encoded small molecule library

Compounds of formula (I) and (II) are disclosed, as well as methods for their identification, their preparation, pharmaceutical compositions containing them, and their use in treating disease. The compounds inhibit the production of TNF-alpha and interleukins (IL) by the inhibition of p38 kinase. They are useful in the treatment of inflammation and arthritis. 

P38 kinase inhibitors

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.

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Bedford, MA, United States of America

Matthew Clark