209 results about "Glycogen synthase" patented technology

The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts,wherein A, R1, R2, R3 and m, are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as Glycogen Synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus Kinases (JAK), Cdc7, AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.

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.

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.

The present invention relates to a new use of oxindole derivatives of formula I, as a free base or pharmaceutically acceptable salts thereof, in the manufacture of a medicament for the prevention and / or treatment of dementia related diseases, Alzheimer's Disease and conditions associated with glycogen synthase kinase-3. Formula (I) wherein R1, R2, R3, ring Z, m and n are as defined as in claim 1. The present invention further relates to a method of prevention and / or treatment of dementia related diseases, Alzheimer's Disease and conditions associated with glycogen synthase kinase-3, as well as a pharmaceutical composition for said use.

Provided are a method for inducing the transdifferentiation of somatic cells into neural stem cells and application for same. Using a combination of a histone deacetylase (HDAC) inhibitor, a glycogen synthase kinase (GSK-3) inhibitor, and a transforming growth factor β (TGF-β) signal pathway inhibitor, in a low-oxygen normal physiological environment, induce somatic cells such as fibroblasts and epithelial cells to form into neural stem cells having good pluripotency and passage stability.

The invention provides compounds of the formula (I):The compounds have activity against cyclin dependent kinases, glycogen synthase kinase and Auroa kinases and are therefore useful to treat cancer and viral diseases.

The present invention relates to compounds of formula (I) or pharmaceutical acceptable salts,wherein A, R1, R2, R3 and m, are defined in the description. The present invention relates also to methods of making said compounds, and compositions containing said compounds which are useful for inhibiting kinases such as Glycogen Synthase kinase 3 (GSK-3), Rho kinase (ROCK), Janus Kinases (JAK), Cdc7, AKT, PAK4, PLK, CK2, KDR, MK2, JNK1, aurora, pim 1 and nek 2.

The present invention relates to a new compound of formula (I)6-(5-cyano-2-hydroxy-1H-indol-3-yl)pyridine-3-carboxylic acid or a pharmaceutically acceptable salt thereof, in an essentially pure and isolated form, pharmaceutical formulations containing said compounds, to the use of said active compounds in therapy, and methods of prevention and / or treatment of conditions associated with glycogen synthase kinase-3 related disorders, comprising administering to a mammal, including human in need of such prevention and / or treatment, a therapeutically effective amount of said compound, as well as a process for preparing said compound.

Compounds of general formula (I): where A, E, G, X, Y and the bond - - - take various meanings are of use in the preparation of a pharmaceutical formulation, for example in the treatment of a disease in which GSK-3 is involved, including Alzheimer's disease or the non-dependent insulin diabetes mellitus, or hyperproliferative disease such as cancer, displasias or metaplasias of tissue, psoriasis, arteriosclerosis or restenosis.

The invention provides compounds of the formula (0) or salts or tautomers or N-oxides or solvates thereof for use in the prophylaxis or treatment of disease states and conditions such as cancers mediated by cyclin-dependent kinase and glycogen synthase kinase-3. In formula (0): X is a group R1-A-NR4— or a 5- or 6-membered carbocyclic or heterocyclic ring; A is a bond, SO2, C═O, NRg(C═O) or O(C═O) wherein Rg is hydrogen or C1-4 hydrocarbyl optionally substituted by hydroxy or C1-4 alkoxy; Y is a bond or an alkylene chain of 1, 2 or 3 carbon atoms in length; R1 is hydrogen; a carbocyclic or heterocyclic group having from 3 to 12 ring members; or a C1-8 hydrocarbyl group optionally substituted by one or more substituents selected from halogen (e.g. fluorine), hydroxy, C1-4 hydrocarbyloxy, amino, mono- or di-C1-4 hydrocarbylamino, and carbocyclic or heterocyclic groups having from 3 to 12 ring members, and wherein 1 or 2 of the carbon atoms of the hydrocarbyl group may optionally be replaced by an atom or group selected from O, S, NH, SO, SO2; R2 is hydrogen; halogen; C1-4 alkoxy (e.g. methoxy); or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy); R3 is selected from hydrogen and carbocyclic and heterocyclic groups having from 3 to 12 ring members; and R4 is hydrogen or a C1-4 hydrocarbyl group optionally substituted by halogen (e.g. fluorine), hydroxyl or C1-4 alkoxy (e.g. methoxy).

The present invention relates generally to the field of molecular biology and concerns a method for improving plant growth characteristics relative to corresponding wild type plants. More specifically, the present invention concerns a method for improving plant growth characteristics comprising modulating expression in a plant of a nucleic acid encoding a class I homeodomain leucine zipper (HDZip) hox5 polypeptide or a homologue thereof; or comprising modulating expression in a plant of a nucleic acid encoding a nitrate transporter protein (NRT) or a homologue thereof; or comprising modulating expression in a plant of a nucleic acid encoding a polypeptide denoted Yield Enhancing Protein 16 (YEP16); or comprising modulating expression in a plant of a Group I glycogen synthase kinase (Group I shaggy-like kinase) or a homologue thereof. The present invention also concerns plants having modulated expression of a nucleic acid encoding a class I HDZip hox5 polypeptide or a homologue thereof; or having modulated expression of a nucleic acid encoding a NRT protein or a homologue thereof; or having modulated expression of a nucleic acid encoding a polypeptide denoted YEP16; or having modulated expression of a Group I shaggy-like kinase or a homologue thereof, which plants have improved growth characteristics relative to corresponding wild type plants. The invention also provides constructs useful in the methods of the invention.

Novel peptide inhibitors of GSK-3, compositions containing same and uses thereof are disclosed. The novel peptide inhibitors are substrate-competitive inhibitors and have an amino acid sequence designed so as to bind to a defined binding site subunit in GSK-3. Also disclosed are GSK-3 substrate competitive inhibitors which bind to the defined binding site subunit in the enzyme. Also disclosed are mutants of GSK-3 and uses thereof for identifying a putative GSK-3 substrate competitive inhibitor.

Provided herein are compounds of the formula (I):as well as pharmaceutically acceptable salts thereof, wherein the substituents are as those disclosed in the specification. These compounds, and the pharmaceutical compositions containing them, are useful for the treatment of metabolic diseases and disorders such as, for example, type II diabetes mellitus.

Presented herein are methods of generating a multipotent or immature cell from a mature somatic cell, involving contacting a mature somatic cell with one or more small molecule compounds selected from: a histone deacetylase (HDAC) inhibitor; a glycogen synthase kinase 3 (GSK-3) inhibitor; one or more transforming growth factor-beta receptor (TGF-βR) inhibitors; one or more lysine-specific demethylase 1 (LSD1) inhibitors; a cAMP agonist; a histone lysine methyltransferase (EZH2) inhibitor; and a histone methyltransferase (HMTase) G9a inhibitor; valproic acid. Also provided are methods of generating a multipotent or immature cell from a somatic cell, by driving expression of OCT4, or an OCT4 functional homolog or derivative, under the control of a high expressing promoter. Presented herein are also methods of stem cell expansion, stem cell regeneration and differentiation, which comprise contacting stem cells with one or more small chemical compounds.

The invention provides a culture system which contains defined components and efficiently acquires induced pluripotent stem cells (iPS cells) from somatic cells. The culture medium additive provided by the invention contains vitamin C, vitamin B12, insulin, glycogen synthase kinase-3 inhibitor, receptor tyrosine kinase and antioxidant. The culture medium additive provided by the invention can also contain a substituted serum cell growth promoter. The invention also provides a complete medium acquired by inducing pluripotent stem cells, which is prepared from one or more of basic culture medium, serum and substituted serum additive and the culture medium additive. The culture system provided by the invention does not have serum, has no animal source pollution, contains defined chemical components, efficiently acquires iPS cells, can maintain cell growth and proliferation in the process of conversion from somatic cells to iPS cells under the condition that feeder cells do not exist, simultaneously accelerates the induction course of the iPS cells obviously, and greatly improves the efficiency of inducing the somatic cells into the iPS cells.

The present invention provides a method for diagnosing a disease or disorder associated with aberrant GSK-3β expression and / or activity or for determining the predisposition of a subject to the disease or disorder. In particular, the methods of the present invention comprise detecting a marker that comprises one or more polymorphisms and / or one or more allelic variants of a glycogen synthase kinase 3β gene. The present invention also relates to a method for identifying new markers that are diagnostic of a disease or disorder associated with aberrant GSK-3β expression and / or activity. Furthermore, the present invention relates to methods of identifying and producing candidate compounds for the treatment of a disease or disorder associated with aberrant GSK-3β expression and / or activity.

Compounds and compositions including 6-bromo-indirubin, 5-amino-indirubin and N-methyl-indirubins and related indirubin derivatives are provided that are useful as selective modulators of glycogen synthase kinase-3, cyclin-dependent protein kinases or aryl hydrocarbon receptors. Methods of inhibiting or modulating cell growth or cell cycling are provided using the compounds of the invention. In other aspects, compounds and methods for the treatment of protozoan-mediated diseases, Alzheimer's disease and diabetes are provided.

The present invention relates to novel heterocyclic compounds which are useful for inhibiting glycogen synthase kinase 3 (GSK-3), methods of making the compounds, compositions containing the compounds, and methods of treatment using the compounds.

An object of the present invention is to provide a nerve regenerating drug, an agent for the promotion of neuropoiesis of a neural stem cell, a neuron obtained by culturing a neural stem cell in the presence of the agent for the promotion of neuropoiesis, and a method of the manufacture of the neuron. In order to achieve the object, the invention provides a nerve regenerating drug comprising a substance that inhibits the activity of glycogen synthase kinase-3, as an active ingredient; an agent for the promotion of neuropoiesis of a neural stem cell comprising the substance as an active ingredient; a neuron obtained by culturing a neural stem cell in the presence of the agent for the promotion of neuropoiesis; and a method of the manufacture of the neuron. The medical drug according to the invention is useful as a therapeutic drug for neurological diseases such as Parkinson's disease, Alzheimer's disease, Down's disease, cerebrovascular disorder, cerebral stroke, spinal cord injury, Huntington's chorea, multiple sclerosis, amyotrophic lateral sclerosis, epilepsy, anxiety disorder, schizophrenia, depression and manic depressive psychosis.

New bicyclic 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.

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.

Compounds of general Formula (I):wherein R1, R2, R3, Ra, A, B and x are as defined herein are inhibitors of protein kinases in particular members of the cyclin-dependent kinase family and / or the glycogen synthase kinase 3 family and are useful in preventing and / or treating any type of pain, inflammatory disorders, cancer, immunological diseases, proliferative diseases, infectious diseases, cardiovascular diseases, metabolic disorders, renal diseases, neurologic and neuropsychiatric diseases and neurodegenerative diseases.

The invention relates to urea derivatives of formula (I) as inhibitors of glycogen synthase kinase 3β, GSK-3, to processes of preparation of such compounds, to pharmaceutical compositions comprising them, and to their use for the treatment and or prophylaxis of a disease in which GSK-3 is involved, such as Alzheimer's disease or non-insulin dependent diabetes mellitus.

The present invention provides methods for diagnosing a neurological disease and / or for determining the predisposition of a subject to a neurological disease and / or for determining a subject at risk of developing a neurological disease, the method comprising detecting a marker in a glycogen synthase kinase 3β gene or expression product thereof and a microtubule-associated protein tau (MAPT) gene or expression product thereof. The present invention also provides pharmacogenetic methods, e.g., for identifying a subject that will respond to treatment with a therapeutic compound.

Provided is a composition for reprogramming somatic cells to generate embryonic stem cell-like cells, comprising: a) a Bmi1 (B cell-specific Moloney murine leukemia virus integration site 1) protein or a nucleic acid molecule encoding the Bmi1 protein; and b) at least one low molecular weight substance selected from the group consisting of a set of a MEK / ERK (mitogen-activated protein kinase / extracellular regulated kinase) inhibitor and a GSK (glycogen synthase kinase) inhibitor, a set of a G9a HMTase (G9a histone methyltransferase) inhibitor and a DMNT (DNA methyltransferase) inhibitor, and a histone deacetylase inhibitor. Also, a method is provided for reprogramming somatic cells to generate embryonic stem cell-like cells using the composition. In addition to reducing the number of the reprogramming factors conventionally needed, the composition and method allow the generation of pluripotent embryonic stem cell-like cells which have high potential in the cell therapy of various diseases.

The present invention relates generally to the field of molecular biology and concerns a method for improving plant growth characteristics relative to corresponding wild type plants. More specifically, the present invention concerns a method for improving plant growth characteristics comprising modulating expression in a plant of a nucleic acid encoding a class I homeodomain leucine zipper (HDZip) hox5 polypeptide or a homologue thereof; or comprising modulating expression in a plant of a nucleic acid encoding a nitrate transporter protein (NRT) or a homologue thereof; or comprising modulating expression in a plant of a nucleic acid encoding a polypeptide denoted Yield Enhancing Protein 16 (referred to as YEP16); or comprising modulating expression in a plant of a Group I glycogen synthase kinase (Group I shaggy-like kinase) or a homologue thereof. The present invention also concerns plants having modulated expression of a nucleic acid encoding a class I homeodomain leucine zipper (HDZip) hox5 polypeptide or a homologue thereof; or having modulated expression of a nucleic acid encoding a nitrate transporter protein (NRT) or a homologue thereof; or having modulated expression of a nucleic acid encoding a polypeptide denoted Yield Enhancing Protein 16 (hereinafter referred to as YEP16); or having modulated expression of a Group I glycogen synthase kinase (Group I shaggy-like kinase) or a homologue thereof, which plants have improved growth characteristics relative to corresponding wild type plants. The invention also provides constructs useful in the methods of the invention.