Smithkline Beecham Corporation

University of Texas System

Glaxo Wellcome Inc.

Glaxosmithkline LLC

Steven Anthony Kliewer

Timothy Mark Willson

Jurgen M Lehmann

David John Mangelsdorf

Genaro Hernandez

Katie C Coate

Stacey A Jones

Curt Dale Haffner

Patrick Reed Maloney

Julie Beth Stimmel

Derek James Parks

Traci Mansfield

Steven Gerard Blanchard

The present invention relates to the treatment of secretory disorders, and provides novel methods of treatment of these disorders comprising the administration of fibroblast growth factor 21 (FGF21) or derivatives thereof. The methods of the invention are useful in conditions including exocrine pancreatic insufficiency (EPI), for example EPI resulting from cystic fibrosis, alcoholism, pancreatitis, pancreatic cancer, gallstones, celiac disease, high triglycerides, or lupus. The methods of the present invention find further utility in the treatment of salivary flow disorders, for example Sjorgen's syndrome, and the treatment of EPI or pancreatitis resulting from surgical procedures.

Methods and compositions for the treatment of exocrine pancreatic insufficiency

Use of FGF21 in methods of increasing exocrine pancreatic secretion

The present invention relates to a novel human orphan nuclear receptor that binds to a cytochrome P-450 monooxygenase (CYP) promoter and that is activated by compounds that induce CYP gene expression. The invention further relates to nucleic acid sequences encoding such a receptor, to methods of making the receptor and to methods of using the receptor and nucleic acid sequences encoding same. The invention also relates to non-human animals transformed to express the human receptor and to methods of using such animals to screen compounds for drug interactions and toxicities.

Orphan nuclear receptor

Pregnane X receptor method

Methods for the treatment of cholestatic liver disease and reduction and prevention of hepatic injury resulting from cholestasis via administration of a FXR ligand are provided.

Compositions and methods for hepatoprotection and treatment of cholestasis

The present invention includes nuclear receptor heterodimer and nuclear receptor-coactivator peptide assays for identifying ligands for nuclear receptors, utilizing scintillation proximity and fluorescence resonance energy transfer (FRET), and methods of using identified ligands.

Use of FXR ligands

The present invention provides radiolabeled 5-{4-[2-(Methyl-pyridine-2-yl-amino)-ethoxy]-benzyl}-thiazolidine-2,4-dion e. In another aspect, the present invention provides a method for determining whether a compound does or does not interact directly with PPAR-gamma, comprising the step of specifically binding a radiolabeled compound of this invention to the ligand binding domain of PPAR-gamma.

Activators of the nuclear orphan receptor peroxisome

The present invention provides activator compounds, including agonists, to the peroxisome proliferator-activated receptor gamma. Particular PPAR.gamma. activators are set forth, as are a pharmaceutical composition for treating diabetes, non-insulin-dependent diabetes mellitus, cardiovascular disorders, and methods for such treatment.

Growing community of inventors

Dallas, TX, United States of America

Steven Anthony Kliewer