13 results about "Glycogen synthase I" patented technology

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of GYSI RNA in a cell or subject, and in certain instances reducing the amount of GYSI protein in a cell or subject. Such compounds, methods, and pharmaceutical compositions are useful to ameliorate at least one symptom or hallmark of a glycogen storage disease. Such glycogen storage diseases include Lafora disease, adult polyglucosan body disease (APBD), Andersen's disease, and Pompe disease.

Use of glycogen synthase kinase-3 (GSK3) as a protease, and a GSK3-based proteolysis-targeting chimera (PROTAC) and a preparation method and use thereof are provided, belonging to the technical field of proteolysis. The GSK3 and an N-terminal domain, an intermediate domain, or a C-terminal domain thereof have a protease activity and can achieve efficient proteolysis. Based on the GSK3 and other similar proteases, PROTACs can be developed to achieve efficient targeted proteolysis of a target protein.

Disclosed herein are methods for increasing sensitivity of a cancer cell to alternating electric fields by administering an AKT inhibitor, a mammalian target of rapamycin (mTOR) inhibitor, a Phosphatidylinositol 3-Kinase (PI3K) inhibitor, and / or a Glycogen synthase kinase 3β (GSK3β) inhibitor. Disclosed are methods of increasing treatment efficacy comprising applying alternating electric fields to a target site of the subject for a period of time, the alternating electric fields having a frequency and field strength, wherein the target site comprises one or more cancer cells, and administering a therapeutically effective amount of one or more of an mTOR inhibitor, AKT inhibitor, PI3K inhibitor, or GSK3β inhibitor to the subject. Disclosed are methods of reducing viability of cancer cells using alternating electric fields for a period of time, the alternating electric fields having a frequency and field strength in combination with either an mTOR inhibitor, AKT inhibitor, PI3K inhibitor, or GSK3β inhibitor and / or a composition or compound that increases cyclin D1. Disclosed are methods of increasing apoptosis of a cancer cell comprising exposing the cancer cell to alternating electric fields for a period of time, the alternating electric fields having a frequency and field strength; and exposing the cancer cell to a PI3K inhibitor.

The invention discloses an application of glycogen synthase kinase 3beta in preparation of antihypertensive drugs. The GSK3beta gene is inserted into a GV652 plasmid and is packaged into an adeno-associated virus, so that specific overexpression of the adeno-associated virus in vascular endothelial cells is realized, and the adeno-associated virus is used for preparing medicines for treating hypertension. It is found for the first time that overexpression of GSK3beta in endothelial cells can improve the endothelial dependent relaxation function and reduce blood pressure. Mechanism research shows that serine 9-site phosphorylation of GSK3beta can activate an AKT-eNOS signal channel and promote release of nitric oxide, so that the endothelial function is improved, and the antihypertensive effect is achieved. Furthermore, glycine can promote phosphorylation of the GSK3beta Ser9 site, and AKT-eNOS signal activation and NO generation are enhanced. The invention provides a novel anti-hypertension gene therapy strategy for regulating and controlling an endothelial function based on a GSK3beta gene.

Provided herein are compounds of formula (I): (G1-Z1)-L-(G2-Z2), or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein G1, G2, Z1, Z2, and L, are as defined elsewhere herein. Also provided herein are methods of preparing compounds of formula (I). Also provided herein are methods of inhibiting GYS1 and methods of treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

The invention relates generally to field of cancer biology. Provided herein are methods of inhibiting epithelial-mesenchymal transition (EMT) and for inhibiting or preventing metastasis in a cancer cell, the methods comprising contacting the cancer cell with an effective amount of a histone deacetylase 6 (HDAC6) inhibitor and a glycogen synthase kinase-3[3 (GSK30) inhibitor. Methods of screening for an inhibitor of EMT comprising a reporter cell line, which comprises a ZEB1 inducible construct, and an epithelial gene reporter construct are also provided herein.

The invention relates to application of sulfated glycogen synthase kinase-3 in prevention and treatment of liver insulin resistance. Specifically, the invention provides an application of a hyposulfated GSK-3beta inhibitor in preparation of a medicine, and the medicine is used for preventing or treating insulin resistance; the invention further discloses application of the GSK-3beta knockout reagent in preparation of a medicine. The medicine is used for preventing or treating insulin resistance.

Provided herein are methods of determining a total number of mutations in at least one gene in a biological sample obtained from a subject suffering from pancreatic cancer, and, based on the total number of mutations: (a) selecting a patient for treatment with a glycogen synthase kinase-3 inhibitor; (b) treating a patient with a glycogen synthase kinase-3 inhibitor; and / or (c) continuing to treat a subject with a glycogen synthase kinase-3 inhibitor.

Novel compounds of formula I and compositions thereof, which are inhibitors of glycogen synthase kinase 3 beta (GSK3 beta). Certain aspects of the present invention relate to novel compounds and compositions having better pharmacokinetic profiles than previous GSK3 [beta] inhibitors, and the pharmacokinetic profiles are more suitable for therapeutic use.

A method for treating cancer in a pediatric patient requiring treatment is provided, comprising administering 9-ING-41 to the patient in combination with an additional therapeutic agent.

Provided herein are compounds of formula (I) or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, n, R1, R2, R3, R4, Y1, Y2, X1, X2, L, and Q1 are as defined elsewhere herein. Also provided herein CN are methods of preparing compounds of formula (I). Also provided herein are methods of inhibiting GYSI and methods of treating a GYS1-mediated disease, disorder, or condition in an individual in need thereof.

The invention provides a property-changed glycogen synthase mutant and application thereof, and relates to the technical field of enzyme engineering. According to the invention, rational design and site-directed mutagenesis are carried out on wild glycogen synthase, so that an enzyme mutant with enhanced heat resistance is obtained. Compared with a wild-type enzyme, the mutant shows remarkably improved catalytic activity in a temperature range of 30-46 DEG C, effectively overcomes the application bottleneck that a natural enzyme is easy to inactivate under a mild hot condition, can efficiently catalyze an alpha-1, 4-glucosidic bond synthesis reaction taking ADP-glucose as a donor, and has a wide application prospect. The lactic acid can be used as a core biocatalyst for constructing a stable multi-enzyme catalysis system, and shows excellent industrial application prospects in green synthesis of bio-based chemicals represented by lactic acid.

The invention belongs to the technical field of biological medicine, and relates to a method for preparing PAPA / siRNA nanoparticles by adopting a delivery carrier PAH-AM-PEG-ApoE (159-167) 2 (PAPA) modified by apolipoprotein E (ApoE) peptide through an electrostatic binding self-assembly method by designing and screening a siRNA sequence aiming at beta-site amyloid precursor protein cutting enzyme 1 (BACE1) and glycogen synthase kinase-3beta (GSK3beta) and adopting a delivery carrier PAH-AM-PEG-ApoE (159-167) 2 (PAPA) modified by ApoE peptide. The siRNA nano delivery system constructed by the invention aims to explore a new way for AD treatment.