Abstract: The invention includes a thioamide-modified peptide, wherein the thioamide modification increases the in vivo half-life of the peptide. The invention further includes methods of treating or preventing a disease or disorder in a subject in need thereof, the method comprising administering to the subject a thioamide-modified peptide of the invention.

Abstract: The invention provides, inter alia, fatty acyl hydroxy fatty acid (FAHFA; a novel class of estolide-related molecules) and diagnostic and treatment methods for a variety of disorders—including diabetes-related disorders, Metabolic Syndrome, polycyctic ovarian syndrome, cancer, and inflammatory disorders—using them; as well as methods of screening for additional compounds that are useful in treating these disorders and/or that modulate FAHFA levels, FAHFA-mediated signaling, and FAHFA-mediated biological effects.

Abstract: The invention includes a thioamide-modified peptide, wherein the thioamide modification increases the in vivo half-life of the peptide. The invention further includes methods of treating or preventing a disease or disorder in a subject in need thereof, the method comprising administering to the subject a thioamide-modified peptide of the invention.

Abstract: Provided herein are methods for treating type 1 diabetes and its sequelae (e.g., cardiovascular, renal or neurologic diseases for which type 1 diabetes is a risk factor) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a fatty acid ester of a hydroxy fatty acid (FAHFA), or a pharmaceutically acceptable salt thereof.

Abstract: The invention includes a thioamide-modified peptide, wherein the thioamide modification increases the in vivo half-life of the peptide. The invention further includes methods of treating or preventing a disease or disorder in a subject in need thereof, the method comprising administering to the subject a thioamide-modified peptide of the invention.

Abstract: Described herein are peptide analogs of glucagon-like peptide 1 (GLP-1) that retain agonist activity, but are more resistant to proteolytic degradation than native GLP-1. In the analogs, at least one ?-amino acid found in the native GLP-1 is replaced with a ?-amino acid residue, which may or may not be cyclically constrained. Pharmaceutical compositions containing the analogs are described, as are methods to treat diabetes, and methods to make proteolytically resistant GLP-1 analogs.

Abstract: The invention provides, inter alia, fatty acyl hydroxy fatty acid (FAHFA; a novel class of estolide-related molecules) and diagnostic and treatment methods for a variety of disorders—including diabetes-related disorders, Metabolic Syndrome, polycystic ovarian syndrome, cancer, and inflammatory disorders—using them; as well as methods of screening for additional compounds that are useful in treating these disorders and/or that modulate FAHFA levels, FAHFA-mediated signaling, and FAHFA-mediated biological effects.

Abstract: Provided herein are methods for treating type 1 diabetes and its sequelae (e.g., cardiovascular, renal or neurologic diseases for which type 1 diabetes is a risk factor) in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a fatty acid ester of a hydroxy fatty acid (FAHFA), or a pharmaceutically acceptable salt thereof.

Abstract: The invention includes a thioamide-modified peptide, wherein the thioamide modification increases the in vivo half-life of the peptide. The invention further includes methods of treating or preventing a disease or disorder in a subject in need thereof, the method comprising administering to the subject a thioamide-modified peptide of the invention.

Abstract: The invention includes a thioamide-modified peptide, wherein the thioamide modification increases the in vivo half-life of the peptide. The invention further includes methods of treating or preventing a disease or disorder in a subject in need thereof, the method comprising administering to the subject a thioamide-modified peptide of the invention.

Abstract: The invention provides, inter alia, fatty acyl hydroxy fatty acid (FAHFA; a novel class of estolide-related molecules) and diagnostic and treatment methods for a variety of disorders—including diabetes-related disorders, Metabolic Syndrome, polycyctic ovarian syndrome, cancer, and inflammatory disorders—using them; as well as methods of screening for additional compounds that are useful in treating these disorders and/or that modulate FAHFA levels, FAHFA-mediated signaling, and FAHFA-mediated biological effects.

Abstract: Described herein are peptide analogs of glucagon-like peptide 1 (GLP-1) that retain agonist activity, but are more resistant to proteolytic degradation than native GLP-1. In the analogs, at least one ?-amino acid found in the native GLP-1 is replaced with a ?-amino acid residue, which may or may not be cyclically constrained. Pharmaceutical compositions containing the analogs are described, as are methods to treat diabetes, and methods to make proteolytically resistant GLP-1 analogs.

Abstract: Described herein are peptide analogs of glucagon-like peptide 1 (GLP-1) that retain agonist activity, but are more resistant to proteolytic degradation than native GLP-1. In the analogs, at least one ?-amino acid found in the native GLP-1 is replaced with a ?-amino acid residue, which may or may not be cyclically constrained. Pharmaceutical compositions containing the analogs are described, as are methods to treat diabetes, and methods to make proteolytically resistant GLP-1 analogs.

Abstract: Macrocyclic compounds that specifically inhibit insulin degrading enzyme (IDE) are provided. Pharmaceutically acceptable salts, solvates, hydrates, stereoisomers, polymorphs, tautomers, isotopically enriched forms, and prodrugs of the macrocyclic IDE inhibitors are also described. Pharmaceutical compositions are also provided. In vivo and in vitro methods of using the IDE inhibitor, and pharmaceutical compositions comprising the IDE inhibitor, for example, for the inhibition of IDE in a subject exhibiting aberrant IDE activity, impaired insulin signaling, or insulin resistance, for example, a subject having diabetes, are also provided.

Abstract: The invention includes a thioamide-modified peptide, wherein the thioamide modification increases the in vivo half-life of the peptide. The invention further includes methods of treating or preventing a disease or disorder in a subject in need thereof, the method comprising administering to the subject a thioamide-modified peptide of the invention.

Abstract: IDE-binding probes and assays for the identification of IDE-binding and IDE-inhibiting compounds are provided. Pharmaceutical compositions of macrocyclic IDE inhibitors are also provided, including compositions in which such IDE inhibitors are combined with an additional therapeutic agent. Methods of using IDE inhibitors for transiently inhibiting IDE in a subject in need thereof, for example, for the transient inhibition of IDE in a subject exhibiting aberrant IDE activity, impaired isulin signaling, or insulin resistance, for example, a subject having diabetes, are also provided. Methods of using IDE inhibitors for transiently modulating heart rate and/or blood pressure in a subject are also provided.

Abstract: The invention provides, inter alia, fatty acyl hydroxy fatty acid (FAHFA; a novel class of estolide-related molecules) and diagnostic and treatment methods for a variety of disorders—including diabetes-related disorders, Metabolic Syndrome, polycystic ovarian syndrome, cancer, and inflammatory disorders—using them; as well as methods of screening for additional compounds that are useful in treating these disorders and/or that modulate FAHFA levels, FAHFA-mediated signaling, and FAHFA-mediated biological effects.

Abstract: Macrocyclic compounds that specifically inhibit insulin degrading enzyme (IDE) are provided. Pharmaceutically acceptable salts, solvates, hydrates, stereoisomers, polymorphs, tautomers, isotopically enriched forms, and prodrugs of the macrocyclic IDE inhibitors are also described. Pharmaceutical compositions are also provided. In vivo and in vitro methods of using the IDE inhibitor, and pharmaceutical compositions comprising the IDE inhibitor, for example, for the inhibition of IDE in a subject exhibiting aberrant IDE activity, impaired insulin signaling, or insulin resistance, for example, a subject having diabetes, are also provided.

Abstract: Macrocyclic compounds that specifically inhibit insulin degrading enzyme (IDE) are provided. Pharmaceutically acceptable salts, solvates, hydrates, stereoisomers, polymorphs, tautomers, isotopically enriched forms, and prodrugs of the macrocyclic IDE inhibitors are also described. Pharmaceutical compositions are also provided. In vivo and in vitro methods of using the IDE inhibitor, and pharmaceutical compositions comprising the IDE inhibitor, for example, for the inhibition of IDE in a subject exhibiting aberrant IDE activity, impaired insulin signaling, or insulin resistance, for example, a subject having diabetes, are also provided.

Abstract: The invention provides, inter alia, fatty acyl hydroxy fatty acid (FAHFA; a novel class of estolide-related molecules) and diagnostic and treatment methods for a variety of disorders—including diabetes-related disorders, Metabolic Syndrome, polycyctic ovarian syndrome, cancer, and inflammatory disorders using them; as well as methods of screening for additional compounds that are useful in treating these disorders and/or that modulate FAHFA levels, FAHFA-mediated signaling, and FAHFA-mediated biological effects.