Abstract: The present invention is directed to the bifunctional compounds and the use of such bifunctional compounds to lower plasma levels of extracellular target molecules by lysosomal degradation. Such bifunctional compounds have a cell surface receptor ligand covalently linked to a ligand that is capable of binding to an extracellular target molecule (such as a ligand for a growth factor, a cytokine, a chemokine, a hormone, a neurotransmitter, a capsid, a soluble receptor, an extracellular secreted protein, an antibody, a lipoprotein, an exosome, a virus, a cell, or a plasma membrane protein), where the cell surface receptor is associated with receptor mediated endocytosis, including asialoglycoprotein receptor (ASGPR) mediated lysosomal degradation and mannose-6-phosphate (M6PR) mediated lysosomal degradation.

Abstract: The present invention provides compounds of formula (IV); or pharmaceutically acceptable salts thereof, wherein the variables are defined as herein. The present invention provides a method for manufacturing the compounds of formula (IV), their therapeutic uses, combinations with other of pharmacologically active agents, and a pharmaceutical compositions.

Abstract: The present invention provides compounds of formula (I); or pharmaceutically acceptable salts thereof, wherein the variables are defined as herein. The present invention provides a method for manufacturing the compounds of formula (I), their therapeutic uses, combinations with other of pharmacologically active agents, and a pharmaceutical compositions.

Abstract: The present invention provides compounds of formula (I); or pharmaceutically acceptable salts thereof, wherein the variables are defined as herein. The present invention provides a method for manufacturing the compounds of formula (I), their therapeutic uses, combinations with other of pharmacologically active agents, and a pharmaceutical compositions.

Abstract: The present invention provides compounds of formula (I); or pharmaceutically acceptable salts thereof, wherein the variables are defined as herein. The present invention provides a method for manufacturing the compounds of formula (I), their therapeutic uses, combinations with other of pharmacologically active agents, and a pharmaceutical compositions.

Abstract: This invention provides peptides with novel modifications that provide suitable derivatization sites to improve the pharmacokinetic properties of the peptides. These modified peptides function in vivo as agonists of the VPAC2 receptor. The peptides of the present invention provide a new therapy for patients with decreased endogenous insulin secretion, for example, type 2 diabetics.

Abstract: This invention provides novel peptides that function in vivo as agonists of the VPAC2 receptor. These insulin secretagogue polypeptides are shown to lower blood glucose in vivo more than controls upon glucose challenge. The polypeptides of this invention are also stable in formulation and have long half-lives. The peptides of the present invention provide a new therapy for patients with decreased endogenous insulin secretion, in particular type 2 diabetics. In particular, the invention is a polypeptide selected from a specific group of VPAC2-related polypeptides, or functional equivalents thereof. The invention is also directed to a method of treating a metabolic disease in a mammal comprising administering a therapeutically effective amount of the insulin secretagogue peptides to said mammal. Also disclosed are methods of making the peptides, both recombinant and synthetic.

Abstract: The invention provides polypeptides that act both as an agonist of the GLP-1 receptor and an antagonist of the glucagon receptor. Such polypeptides are useful for treating individuals with type 2 diabetes or other metabolic disorders.

Abstract: The invention provides polypeptides that act both as an agonist of the GLP-1 receptor and an antagonist of the glucagon receptor. Such polypeptides are useful for treating individuals with type 2 diabetes or other metabolic disorders.

Abstract: The invention provides polypeptides that act both as an agonist of the GLP-1 receptor and an antagonist of the glucagon receptor. Such polypeptides are useful for treating individuals with type 2 diabetes or other metabolic disorders.

Abstract: The invention provides polypeptides that act both as an agonist of the GLP-1 receptor and an antagonist of the glucagon receptor. Such polypeptides are useful for treating individuals with type 2 diabetes or other metabolic disorders.

Abstract: The invention provides polypeptides that act both as an agonist of the GLP-1 receptor and an antagonist of the glucagon receptor. Such polypeptides are useful for treating individuals with type 2 diabetes or other metabolic disorders.

Abstract: The invention provides polypeptides that act both as an agonist of the GLP-1 receptor and an antagonist of the glucagon receptor. Such polypeptides are useful for treating individuals with type 2 diabetes or other metabolic disorders.

Abstract: The invention provides polypeptides that act both as an agonist of the GLP-1 receptor and an antagonist of the glucagon receptor. Such polypeptides are useful for treating individuals with type 2 diabetes or other metabolic disorders.