Ardelyx, Inc.

Sunesis Pharmaceuticals, Inc.

Vicuron Pharmaceuticals Inc.

Glaxo Group Limited

Novartis Ag

University of Colorado

Affymetrix, Inc.

Affymax Technologies, N.v.

Jeffrey William Jacobs

Dominique Charmot

Michael Robert Leadbetter

Christopher Carreras

Noah Bell

Jason Gustaf Lewis

Eric Labonte

Marc Navre

Tao Chen

Han-Ting Chang

Nicholas Reich

Ingrid Langsetmo

Rakesh K Jain

Robert C Blanks

James Prentice Davidson

Natalia Blinova

Fangling Lin

Dinesh Vinoobhai Patel

Dean R Dragoli

Zhengyu Yuan

Anantha R Sudhakar

Marc Evanchik

Matthew John Siegel

Jeffrey A Silverman

Jeremy Caldwell

Jason G Lewis

Daniel C Adelman

Patricia Finn

Zhi-Jie Ni

Valery V Antonenko

Nicolay V Kulikov

Glenn H McGall

Marvin H Caruthers

Steven A Sundberg

Min Zhong

Wenjin Yang

Christopher P Holmes

David A Campbell

Hua Yang

Irina Dotsenko

Matthew Siegel

Andrew King

Wanli Lu

Douglas R Cary

John Robert Schullek

David Fujimoto

Ying He

Rakesh K Patel

Jian Sun

Yafan Lu

Darla A Graff

Edward Timofeey

Andrei Mirzabekov

Xunxiang Du

Johan Oslob

The invention relates to non-systemic TGR5 agonist useful in the treatment of chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition especially during short bowel syndrome, and irritable bowel syndrome (IBS), and other TGR5 associated diseases and disorders, having the Formula:

Substituted 4-phenyl pyridine compounds as non-systemic TGR5 agonists

The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders. The methods generally comprise administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that is designed to be substantially active in the gastrointestinal (GI) tract to inhibit NHE-mediated antiport of sodium ions and hydrogen ions therein. More particularly, the method comprises administering to a mammal in need thereof a pharmaceutically effective amount of a compound, or a pharmaceutical composition comprising such a compound, that inhibits NHE-3, -2 and/or -8 mediated antiport of sodium and/or hydrogen ions in the GI tract and is designed to be substantially impermeable to the layer of epithelial cells, or more specifically the epithelium of the GI tract. As a result of the compound being substantially impermeable, it is not absorbed and is thus essentially systemically non-bioavailable, so as to limit the exposure of other internal organs (e.g., liver, heart, brain, etc.) thereto. The present disclosure is still further directed to a method wherein a mammal is administered such a compound with a fluid-absorbing polymer, such that the combination acts as described above and further provides the ability to sequester fluid and/or salt present in the GI tract.

Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders

Provided are non-NHE3-binding agents having activity as phosphate transport/uptake inhibitors in the gastrointestinal tract, including in the small intestine, methods for their use as therapeutic or prophylactic agents, and related methods of drug discovery.

Compounds and methods for inhibiting phosphate transport

The invention relates to non-systemic TGR5 agonist useful in the treatment of chemotherapy-induced diarrhea, diabetes, Type II diabetes, gestational diabetes, impaired fasting glucose, impaired glucose tolerance, insulin resistance, hyperglycemia, obesity, metabolic syndrome, ulcerative colitis, Crohn's disease, disorders associated with parenteral nutrition especially during short bowel syndrome, and irritable bowel syndrome (IBS), and other TGR5 associated diseases and disorders, having the Formula: where R, R, R, R, R, X, X, X, X, Q, and n are described herein.

Provided are NHE3-binding and/or NHE3-modulating agents having activity as phosphate transport inhibitors, including inhibitors of phosphate transport in the gastrointestinal tract and the kidneys, and methods for their use as therapeutic or prophylactic agent.

NHE3-binding compounds and methods for inhibiting phosphate transport

The present disclosure is directed to compounds and methods for the treatment of disorders associated with fluid retention or salt overload, such as heart failure (in particular, congestive heart failure), chronic kidney disease, end-stage renal disease, liver disease, and peroxisome proliferator-activated receptor (PPAR) gamma agonist-induced fluid retention. The present disclosure is also directed to compounds and methods for the treatment of hypertension. The present disclosure is also directed to compounds and methods for the treatment of gastrointestinal tract disorders, including the treatment or reduction of pain associated with gastrointestinal tract disorders.

The present invention is directed to compositions and methods of removing potassium or treating hyperkalemia by administering pharmaceutical compositions of cation exchange polymers with low crosslinking for improved potassium excretion and for beneficial physical properties to increase patient compliance.

Compositions and methods for treating hyperkalemia

Compounds and compositions for treating, preventing or managing cancer are disclosed. The compositions provided herein comprise SNS-595 and N-desmethyl-SNS-595. Also provided are pharmaceutical compositions comprising the compounds and methods of treatment using the compounds and compositions.

Compounds and compositions for treatment of cancer

Growing community of inventors

San Mateo, CA, United States of America

Jeffrey William Jacobs