Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3? and GSK3? polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: Methods of inhibiting various enzymes and treating various conditions are provided that include administering to a subject a compound of Structure I or IB, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I and IB have the following structures and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting various enzymes and for use in treating conditions mediated by such enzymes.

Abstract: This invention relates to methods of treating or preventing bone loss by administering to a human or animal subject pyrimidine and pyridine derivatives that inhibit the activity of glycogen synthase kinase 3 (GSK3), to pharmaceutical compositions containing the compounds, and to the use of the compounds and compositions alone or in combination with other pharmaceutically active agents.

Abstract: The disclosure herein relates to modified ?PKC inhibitory peptides, methods of generating such peptides, and method for using ?PKC inhibitory peptides for the treatment of pain.

Abstract: Methods of inhibiting various enzymes and treating various conditions are provided that include administering to a subject a compound of Structure I or IB, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I and IB have the following structures and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting various enzymes and for use in treating conditions mediated by such enzymes.

Abstract: New pyridine-based compounds of Formula I, compositions, and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3-mediated disorders in vivo are provided. The methods, compounds, and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3? and GSK3? polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3? and GSK3? polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3? and GSK3? polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3? and GSK3? polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: Compounds of formula 1: wherein R1 is alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, or heteroaralkyl, substituted with 0–3 substituents selected from lower alkyl, halo, hydroxy, lower alkoxy, amino, lower alkyl-amino, and nitro; R2 is hydroxy, amino, or lower alkoxy; R3 is H, lower alkyl, lower acyl, lower alkoxy-acyl, or amino-acyl; R4 is H or lower alkyl; and pharmaceutically acceptable salts and esters thereof; are effective inhibitors of GSK3.

Abstract: New pyrimidine or pyridine based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

Abstract: New pyrimidine or pyridine based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as in the treatment of diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

Abstract: Methods of inhibiting various enzymes and treating various conditions are provided that include administering to a subject a compound of Structure I or IB, a pharmaceutically acceptable salt thereof, a tautomer thereof, or a pharmaceutically acceptable salt of the tautomer. Compounds having the Structure I and IB have the following structures and have the variables described herein. Such compounds may be used to prepare medicaments for use in inhibiting various enzymes and for use in treating conditions mediated by such enzymes.

Abstract: Polynucleotide constructs encoding growth factor independent catalytically active membrane targeted PI 3-kinase mutants useful for therapeutic and research purposes are described. In addition, a method for using the polynucleotide constructs to screen for inhibitors of PI 3-kinase, a method for making 3′ phosphorylated inositol phospholipids, methods of reducing cell death after trauma, and methods of overcoming insulin resistance are described.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3&agr; and GSK3&bgr; polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: Polynucleotide constructs encoding growth factor independent catalytically active membrane targeted PI 3-kinase mutants useful for therapeutic and research purposes are described. In addition, a method for using the polynucleotide constructs to screen for inhibitors of PI 3-kinase, a method for making 3′ phosphorylated inositol phospholipids, methods of reducing cell death after trauma, and methods of overcoming insulin resistance are described.

Abstract: New pyrimidine or pyridine based compounds, compositions and methods of inhibiting the activity of glycogen synthase kinase (GSK3) in vitro and of treatment of GSK3 mediated disorders in vivo are provided. The methods, compounds and compositions of the invention may be employed alone, or in combination with other pharmacologically active agents in the treatment of disorders mediated by GSK3 activity, such as in the treatment of diabetes, Alzheimer's disease and other neurodegenerative disorders, obesity, atherosclerotic cardiovascular disease, essential hypertension, polycystic ovary syndrome, syndrome X, ischemia, traumatic brain injury, bipolar disorder, immunodeficiency or cancer.

Abstract: The invention provides truncated GSK3 polypeptides capable of crystallization, including GSK3&agr; and GSK3&bgr; polypeptides, and use of these polypeptides to identify and optimize GSK3 inhibitors. Also provided are GSK3 polypeptides having at least one substituted amino acid that differs from wild-type GSK3, wherein the substituted amino acid is incapable of being phosphorylated. The invention finds use in providing methods of identifying and optimizing compounds useful for treating diseases mediated by GSK3 activity, including Alzheimer's disease, type 2 diabetes, and inflammation.

Abstract: The invention is generally directed to compositions and methods for affecting signal transduction using the casein kinase I (CKI) gene or gene product. The invention is more specifically directed to affecting the Wnt signal pathway using the CKI gene or gene product. The invention is particularly directed to using the CKI gene or gene product to treat and diagnose cancer, particularly breast and colon cancer. CKI&egr; is the preferred species. The field of the invention is compositions and methods for modulating signal transduction using the (CKI) gene or gene products and variants thereof. The invention is more specifically directed to modulating the Wnt signal pathway using the CKI gene or gene product. The invention is particularly directed to using the CKI gene or gene product to treat and diagnose disorders mediated by the Wnt signal pathway, especially hyperproliferative disorders, particularly breast and colon cancer.