Abstract: Disclosed are polypeptides, compositions, and methods useful for activating a glucagon-like peptide-1 (GLP-1) receptor and treating or preventing diseases or disorders at least partially mediated by glucagon-like peptide 1 (GLP-1).

Abstract: The present disclose includes, among other things, compounds that treat or lessen the severity of cancer, pharmaceutical compositions and methods of making and using the same.

Abstract: Methods for treating bladder cancer and solid tumors are disclosed. The methods include administering to a patient a compound of formula 1 Pharmaceutical compositions of compound 1 are also disclosed.

Abstract: Disclosed are polypeptides, compositions, and methods useful for activating a glucagon-like peptide-1 (GLP-1) receptor and treating or preventing diseases or disorders at least partially mediated by glucagon-like peptide 1 (GLP-1).

Abstract: The present invention provides compounds of Formula I?: wherein W, X, Y, Z, Z1, Z2, R1, R2, R3, R4 and R5 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are effective at modulating the STING protein and thus can be used as medicaments for treating or preventing disorders affected by the agonism of STING.

Abstract: The present invention provides compounds of Formula I?: wherein , W, X, Y, Z, Z1, Z2, R1, R2, R3, R4 and R5 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are effective at modulating the STING protein and thus can be used as medicaments for treating or preventing disorders affected by the agonism of STING.

Abstract: Methods for treating bladder cancer and solid tumors are disclosed. The methods include administering to a patient a compound of formula 1 Pharmaceutical compositions of compound 1 are also disclosed.

Abstract: Methods for treating bladder cancer and solid tumors are disclosed. The methods include administering to a patient a compound of formula 1 Pharmaceutical compositions of compound 1 are also disclosed.

Abstract: The present invention provides compounds of Formula I?: wherein , W, X, Y, Z, Z1, Z2, R1, R2, R3, R4 and R5 are as defined herein, or a stereoisomer, tautomer, pharmaceutically acceptable salt, prodrug ester or solvate form thereof, wherein all of the variables are as defined herein. These compounds are effective at modulating the STING protein and thus can be used as medicaments for treating or preventing disorders affected by the agonism of STING.

Abstract: N-heterocyclic compounds that block cytokine production via inhibition of p38 kinase are disclosed. In one embodiment, compounds of the present invention are represented by Formula (I): Methods of production, pharmaceutical compositions and methods of treating conditions associated with inappropriate p38 kinase activity or TNF-? expression utilizing compounds of the present invention are also disclosed.

Abstract: Compounds of the formula are disclosed as Mnk2 inhibitors which are useful for the treatment and prevention of metabolic disorders such as obesity and diabetes.

Abstract: Compounds of the formula wherein R1 represents optionally substituted C1-C10 alkyl, aryl or heteroaryl, and R3 represents alkoxy-substituted aryl or optionally substituted heteroaryl, are disclosed as Mnk2 inhibitors which are useful for the treatment and prevention of metabolic disorders such as obesity and diabetes.

Abstract: N-heterocyclic compounds that block cytokine production via inhibition of p38 kinase are disclosed. In one embodiment, compounds of the present invention are represented by Formula (I): Methods of production, pharmaceutical compositions and methods of treating conditions associated with inappropriate p38 kinase activity or TNF-? expression utilizing compounds of the present invention are also disclosed.

Abstract: N-heterocyclic compounds that block cytokine production via inhibition of p38 kinase are disclosed. In one embodiment, compounds of the present invention are represented by Formula (I): Methods of production, pharmaceutical compositions and methods of treating conditions associated with inappropriate p38 kinase activity or TNF-? expression utilizing compounds of the present invention are also disclosed.

Abstract: A high-throughput molecular docking facility is presented for screening combinatorial libraries to identify binding ligands and ultimately pharmaceutical compounds. The facility employs a pre-docking conformational search to generate multiple solution conformations of a ligand. The molecular docking facility includes: generating a binding site image of the protein, the binding site image having multiple hot spots; matching hot spots of the binding site image to atoms in at least one solution conformation of the multiple solution conformations of the ligand to obtain at least one ligand position relative to the protein in a ligand-protein complex formation; and optimizing the at least one ligand position while allowing translation, orientation and rotatable bonds of the ligand to vary, and while holding the protein fixed.

Abstract: A high-throughput molecular docking facility is presented for screening combinatorial libraries to identity binding ligands and ultimately pharmaceutical compounds. The facility employs a pre-coking conformational search to generate multiple solution conformations of a ligand. The molecular docking facility includes: generating a binding site image of the target molecule, the binding site image to atoms in at least one solution conformation of the multiple solution conformations of the ligand to obtain at least one ligand postion relative to the target molecule in a ligand-target molecule complex formation; and optimizing the at least one ligand position while allowing translation, orientation and rotatable bonds of the ligand to vary, and while holding the target molecule fixed. Docking results are clustered using as a metric the rms deviation between the core of two docked molecules.

Abstract: N-heterocyclic compounds that block cytokine production via inhibition of p38 kinase are disclosed.

Abstract: In a computational method of assessing a combinatorial library for complementarity to a target molecule, ligands from the library are first docked to the target molecule. The docking results are clustered using as a metric the rms deviation between the core of two docked molecules. The library is rated as to complementarity to the target molecule according to the relative number of ligands in the top cluster.