The Salk Institute for Biological Studies

The University of Sydney Commercial Development & Industry Partnerships

New York University

Jae Myoung Suh

Ronald Mark Evans

Michael Downes

Johan W Jonker

Annette R Atkins

Ruth T Yu

John F W Keana

Christopher Liddle

Thomas J Baiga

Sungsoon Fang

Moosa Mohammadi

Regina Goetz

Senyon Choe

Witek Kwiatkowski

John FW Keana

Novel compounds having a formula embodiments of a method of making the same, and of a composition comprising them are disclosed herein. Also disclosed are embodiments of a method of treating or preventing a metabolic disorder in a subject, comprising administering to a subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and treating or preventing a metabolic disorder in the subject. Additionally disclosed are embodiments of a method of treating or preventing inflammation in an intestinal region of a subject, comprising administering to the subject (e.g., via the gastrointestinal tract) a therapeutically effective amount of one or more of the disclosed compounds, thereby activating FXR receptors in the intestines, and thereby treating or preventing inflammation in the intestinal region of the subject.

Analogs of fexaramine and methods of making and using

The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidemia, obesity, and fatty liver.

Methods for treating metabolic disorders using FGF

The present disclosure provides chimeric proteins having an N-terminus coupled to a C-terminus, wherein the N-terminus comprises an N-terminal portion of fibroblast growth factor (FGF) 2 and the C-terminus comprises a portion of an FGF1 protein, wherein the chimeric protein comprises at least 95% sequence identity to SEQ ID NO: 9, 10, 11, 12 or 13. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.

Chimeric fibroblast growth factor (FGF) 2/FGF1 peptides and methods of use

The present disclosure provides FGF1 mutant proteins, such as those having an N-terminal deletion, point mutation(s), or combinations thereof, which can reduce blood glucose in a mammal. Such mutant FGF1 proteins can be part of a chimeric protein that includes a &#x3b2;-Klotho-binding protein, an FGFR1c-binding protein, a &#x3b2;-Klotho-binding protein and a FGFR1c-binding protein, a C-terminal region from FGF19 or FGF21. In some examples, mutant FGF1 proteins have reduced mitogenic activity. Also provided are nucleic acid molecules that encode such proteins, and vectors and cells that include such nucleic acids. Methods of using the disclosed molecules to reduce blood glucose levels are also provided.

Mutated fibroblast growth factor (FGF) 1 and methods of use

The method provides methods and compositions for treating metabolic disorders such as impaired glucose tolerance, elevated blood glucose, insulin resistance, dyslipidaemia, obesity, and fatty liver.

The present invention relates to a chimeric protein that includes an N-terminus coupled to a C-terminus, where the N-terminus includes a portion of a paracrine fibroblast growth factor ('FGF') and the C-terminus includes a C-terminal portion of an FGF19 molecule. The portion of the paracrine FGF is modified to decrease binding affinity for heparin and/or heparan sulfate compared to the portion without the modification. The present invention also relates to pharmaceutical compositions including chimeric proteins according to the present invention, methods for treating a subject suffering from diabetes, obesity, or metabolic syndrome, and methods of screening for compounds with enhanced binding affinity for the &#x3b2;Klotho-FGF receptor complex involving the use of chimeric proteins of the present invention.

Growing community of inventors

San Diego, CA, United States of America

Jae Myoung Suh