Srx Cardio, LLC

G.d. Searle & Company

Pharmacia Corporation

Serenex, Inc.

Other

G.d. Searle LLC

Monsanto Company

Esanex, Inc.

Sxr Cardio, LLC

Thomas E Barta

Daniel Paul Becker

John Nicholas Freskos

Joseph J McDonald

Jonathan William Bourne

Gary A DeCrescenzo

Clara I Villamil

Louis J Bedell

Daniel P Getman

Michael Mark Muehlemann

Kyle D Monroe

Anjali Pandey

Susan Landis Hockerman

Terri L Boehm

Simeon Bowers

Brent V Mischke

Gunnar J Hanson

Deborah A Mischke

Joseph Gerace Rico

Richard A Mueller

James Marvin Veal

Yvette M Fobian

Kenneth He Huang

Jeffery N Carroll

Nathan W Stehle

Lindsay A Hinkley

Jeron Eaves

Lifeng Geng

Steve A Kolodziej

Robert M Heintz

William F Vernier

Shashidhar N Rao

Darren J Kassab

Madeleine H Li

John Jeffrey Talley

Michael B Tollefson

Lijuan Jane Wang

Monica B Norton

Patrick B Mullins

Richard M Weier

Richard A Partis

Paul Waddell Collins

John Patrick McKearn

Michael A Stealey

Francis J Koszyk

Susan A Gregory

Susan C Howard

Hui Li

Stephen A Kolodziej

Carol Pearcy Howard

Jeffrey N Carroll

Ish K Khanna

David Louis Brown

Margaret Lanahan Grapperhaus

Mark A Massa

Alan Frank Gasiecki

He Huang

Roy Wendell Ware

Renee Huff

Jiang Zhu

Mark Karbarz

Vesa Nevalainen

Eric T Baldwin

Gary A De Crescenzo

Theresa R Fletcher

Michelle A Schmidt

Emilie Despagnet Smith

Wei Ma

Elizabeth C Arner

Andy Ommen

Yiyuan Chen

Mark A Nagy

Thomas A Wynn

Rao N Shashidhar

Margaret Thompson Reece

Gary A DeCrezcenzo

The present disclosure relates to novel compounds capable of binding to PCSK9, thereby modulating PCSK9 biological activity. Also provided are compositions comprising these compounds, methods of preparing the compounds, and methods for use of the compounds in the treatment of PCSK9-related conditions and diseases.

Compounds for the modulation of proprotein convertase subtilisin/kexin type 9 (PCSK9)

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunctions; thus, there is also utility for small organic compound ligands and can raise LDL levels.

Composition and methods of use of tetrahydroisoquinoline small molecules to bind and modulate PCSK9 protein activity

This invention is related to the field of PCSK9 biology and the composition and methods of use of small organic compounds as ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small organic compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small organic compound ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small organic compound ligands that can raise LDL levels.

Phenylalanine small organic compounds to directly modulate PCSK9 protein activity

Phenylpiperazine proprotein convertase subtilisin/kexin type 9 (PCSK9) modulators and their use

The present disclosure relates to novel compounds, methods, and compositions capable of binding to PCSK9, thereby modulating PCSK9 proprotein convertase enzyme activity, for treatment of a disease or condition mediated, at least in part, by PCSK9. The compounds of the disclosure include compounds Formula (I).

Compounds for binding proprotein convertase subtilisin/kexin type 9

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

Method to treat lipid dysregulation by modulation of proprotein convertase subtilisin/kexin type 9 (PCSK9) protein activity with small molecule ligands

Composition and methods of use of novel phenylalanine small organic compounds to directly modulate PCSK9 protein activity

This invention is related to the field of PCSK9 biology and the composition and methods of use of small molecule ligands for modulation of PCSK9 biological activity. In particular, the invention provides compositions of small molecule compounds that modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9. Binding these small molecule ligands to PCSK9 alters the conformation of the protein, modifying the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for small molecule ligands that can raise LDL levels.

Composition and methods of use of small molecules as binding ligands for the modulation of proprotein convertase subtilisin/kexin type 9(PCSK9) protein activity

This invention is related to the field of hypercholesterolemia. In particular, the invention provides compositions and methods to modulate circulating levels of low density lipoproteins by altering the conformation of the protein PCSK9 using synthetic ligands and/or synthetic ligand derivative sequences of 3-8 amino acids ranging between 350-2,000 Da. Altering the conformation of PCSK9 affects the interaction between PCSK9 and an endogenous low density lipoprotein receptor, and can lead to reduced or increased levels of circulating LDL-cholesterol. High LDL-cholesterol levels are associated with increased risk for heart disease. Low LDL-cholesterol levels may be problematic in other conditions, such as liver dysfunction; thus, there is also utility for ligands which can raise LDL levels.

Proprotein convertase subtilisin kexin type 9 (PCSK9) allosteric binding ligands to modulate serum low density lipoprotein (LDL) levels

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Evanston, IL, United States of America

Thomas E Barta