Abstract: One aspect of the present invention relates to substituted pyridines and pharmaceutically acceptable salts thereof that are active against a range of mammalian maladies. Another aspect of the invention relates to a pharmaceutical composition, comprising a compound of the present invention or a pharmaceutically acceptable salt thereof; and a pharmaceutically acceptable excipient. The present invention also relates to methods of treating a range of mammalian maladies or conditions, including but not limited to hyperlipidemia, hypercholesterolemia, atherosclerosis, coronary artery disease, congestive heart failure, cardiovascular disease, hypertension, coronary heart disease, angina, pellagra, Hartnup's syndrome, carcinoid syndrome, arterial occlusive disease, obesity, hypothyroidism, vasoconstriction, osteoarthritis, rheumatoid arthritis, diabetes, Alzheimer's disease, lipodystrophy, or dyslipidemia, raising serum high-density lipoprotein (HDL) levels, and lowering serum low-density lipoprotein (LDL) levels.

Abstract: The present invention provides methods for modification and regulation of glucagon-like peptide 1 (GLP-1) metabolism by administering therapeutically effective amounts of an inhibitor of dipeptidylpeptidase IV (DPIV) or a pharmaceutically acceptable salt thereof, where the inhibitor has a Ki for inhibition of DPIV of 10 nM or less; and the inhibitor is administered in an amount sufficient to inhibit DPIV proteolysis of GLP-1 but not sufficient to suppress the immune system of the animal.

Abstract: Polypeptide analogs of the invention that include a) a base amino acid sequence at least 80% identical to one of a GLP-1 fragment; and b) amino acid residues attached to the carboxy terminus of the base amino acid sequence, where the analogs have GLP-1-like activity of longer duration than native GLP-1 and/or the GLP-1 receptor has a greater affinity for the analogs than native GLP-1. Other polypeptide analogs of the invention include a) a base amino acid sequence at least 50% identical to a GLP-1 fragment in which the amino acid residue in the base amino acid sequence corresponding to the P?1 residue of GLP-1 is an amino acid analog having a tetrasubstituted C? carbon; and b) amino acid residues attached to the carboxy terminus of the base amino acid sequence, where the analogs have the properties indicated above. The invention also includes methods of treatment where these analogs are administered.

Abstract: The present invention provides peptidomimetics derived from Apolipoprotein A-I, which is useful for beneficially influencing lipid parameters and/or plasma cholesterol levels. The invention also provides pharmaceutical compositions and methods of treatment for elevated levels of plasma cholesterol.

Abstract: The invention provides compounds and methods for inhibiting proteases. One aspect of the invention features pro-soft inhibitors which react with an activating protease to release an active inhibitor moiety in proximity to a target protease. In certain instances, compounds inhibit proteasomes and/or post-proline cleaving enzymes (PPCE), such as dipeptidyl peptidase IV. The compounds of the invention provide a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the targeted protease.

Abstract: The invention generally relates to improved methods for the treatment or prophylaxis in animal subjects (including humans) of autoimmune disorders including Type I diabetes, septic shock, multiple sclerosis, inflammatory bowel disease (IBD) and Crohn's disease.

Abstract: The invention provides compounds and methods for inhibiting proteases. One aspect of the invention features pro-soft inhibitors which react with an activating protease to release an active inhibitor moiety in proximity to a target protease. In certain instances, compounds inhibit proteasomes and/or post-proline cleaving enzymes (PPCE), such as dipeptidyl peptidase IV. The compounds of the invention provide a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the targeted protease. Another aspect of the invention provides for the use of the disclosed compounds for treating Type II diabetes, insulin resistance, glucose intolerance, hyperglycemia, hypoglycemia, hyperinsulinemia, obesity, hyperlipidemia, or hyperlipoproteinemia.

Abstract: The present invention provides methods and compositions for modification and regulation of glucose and lipid metabolism, generally to reduce insulin resistance, hyperglycemia, hyperinsulinemia, obesity, hyperlipidemia, hyperlipoproteinemia (such as chylomicrons, VLDL and LDL), and to regulate body fat and more generally lipid stores, and, more generally, for the improvement of metabolism disorders, especially those associated with diabetes, obesity and/or atherosclerosis.

Abstract: The present invention relates to compositions of peptide and polypeptide analogs that are resistant to proteolysis, pharmaceutical uses thereof, and methods of preparation thereof.

Abstract: The present invention relates to inhibitors of lipases, such as inhibitors of endothelial lipase, as well as pharmaceutical compositions thereof, and methods for using such inhibitors. The prototype of these inhibitors has lipophilic portion and an electrophilic site.

Abstract: Disclosed are 6-(morpholinoalkyl)-substituted pyridines, and pharmaceutically acceptable salts and prodrugs thereof, that are active against a range of mammalian therapeutic indications.

Abstract: Disclosed are peptide-based compounds that include boronic acid or cyano functionality, which efficiently and selectively inhibit fibroblast activation protein alpha. Among other therapeutic utilities, the peptide-based compounds may be useful for the treatment of cancer.

Abstract: Disclosed are heterocyclylalkyl-substituted and heteroaralkyl-substituted pyridines, and pharmaceutically acceptable salts and prodrugs thereof, that are active against a range of mammalian therapeutic indications.

Abstract: The present invention provides peptidomimetics derived from Apolipoprotein A-I, which is useful for beneficially influencing lipid parameters and/or plasma cholesterol levels. The invention also provides pharmaceutical compositions and methods of treatment for elevated levels of plasma cholesterol.

Abstract: The present invention generally provides polypeptide analogues of GLP-‘(9-34) and GLP-1 (9-36) that have increased in vivo half-lives resulting from reduced susceptibility to proteolytic enzymes. Other aspects of the invention relate to methods of using the polypeptide analogues described herein for treating cardiac dysfunction and other heart-related maladies. Yet another aspect of the present invention relates lo formulations comprising the polypeptide analogues described herein.

Abstract: The present invention relates to inhibitors of post-proline cleaving enzymes, such as inhibitors of dipeptidyl peptidase IV, as well as pharmaceutical compositions thereof, and methods for using such inhibitors. In particular, the inhibitors of the present invention are improved over those in the prior art by selection of particular classes of sidechains in the P1 and/or P2 position of the inhibitor that contain a carboxylic acid moiety. The compounds of the present invention can have a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the targeted protease.

Abstract: Disclosed are peptide-based compounds that include boronic acid or cyano functionality, which efficiently and selectively inhibit fibroblast activation protein alpha. Among other therapeutic utilities, the peptide-based compounds may be useful for the treatment of cancer.

Abstract: The present invention relates to compositions of peptide and polypeptide analogs that are resistant to proteolysis, pharmaceutical uses thereof, and methods of preparation thereof.

Abstract: The present invention provides methods and compositions for modification and regulation of glucose and lipid metabolism, generally to reduce insulin resistance, hyperglycemia, hyperinsulinemia, obesity, hyperlipidemia, hyperlipoprotein-emia (such as chylomicrons, VLDL and LDL), and to regulate body fat and more generally lipid stores, and, more generally, for the improvement of metabolism disorders, especially those associated with diabetes, obesity and/or atherosclerosis.

Abstract: The present invention relates to inhibitors of post-proline cleavage enzymes, such as inhibitors of dipeptidyl peptidase IV, as well as pharmaceutical compositions thereof, and methods for using such inhibitors. In particular, the inhibitors of the present invention are improved over those in the prior art by selection of particular classes of side chains in the P1 and/or P2 position of the inhibitor. The compounds of the present invention can have a better therapeutic index, owing in part to reduced toxicity and/or improved specificity for the targeted protease.