26 results about "Glycogen synthase" 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 relates to the technical field of biotechnology and immunotherapy, and discloses a method for inducing and amplifying pMHC specific homologous TSCM, which comprises the following steps: a) preparing pMHC presenting a single antigen peptide; b) sorting lymphocytes and mononuclear cells from a donor, and connecting the pMHC presenting the single antigen peptide obtained in the step a) to the surface of the separated mononuclear cells as stimulating cells; c) co-culturing the sorted lymphocytes serving as effector cells and stimulated cells in a culture medium containing a glycogen synthase kinase-3beta inhibitor, and inducing to generate pMHC specific homogeneous TSCM; and d) separating the pMHC specific homologous TSCM obtained in the step c). The method can induce and amplify sufficient pMHC specific homogeneous TSCM for adoptive immunotherapy, overcomes self tolerance and avoids or alleviates GVHD (Growth Vitamin Horse Disease); the preparation method is simple, induction and amplification efficiency is high, and universality and flexibility are achieved.

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.

Provided herein are compounds of formula (I′):or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y2, Y3, L1, L2, X1, X2, X3, X4, X5, Q1, R1, R2, Rk, Rm, and Rn 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 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 compounds of formula (I): or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein m, n, Y1, Y2, X1, X2, X3, Q1, and Ra are as defined elsewhere herein. Also provided herein 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.

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.

A novel compound of formula I and its composition are provided, which is an inhibitor of glycogen synthase kinase 3-beta (GSK3β). Some aspects of the present invention relate to novel compounds and compositions having a superior pharmacokinetic profile compared to conventional GSK3β inhibitors and a pharmacokinetic profile more suitable for therapeutic applications. [Formula 1] TIFF2026529053000089.tif17159

The present invention refers to an in vitro or ex vivo method for reversing and / or reducing and / or inhibiting the endothelial to mesenchymal transition (EnMT) process in corneal endothelial cells, preferably in primary and / or human corneal endothelial cells, more preferably primary human corneal endothelial cells (HCEnCs), said method comprising the step of incubating said cells with at least one inhibitor of glycogen synthase kinase 3 (GSK-3).

The invention relates to the technical field of biological treatment of bone metabolic diseases, and discloses an application of a bone-strengthening and blood-generating oral liquid in preparation of a medicine for treating osteoporotic fracture.The application includes the steps that when the medicine is prepared, active components in the bone-strengthening and blood-generating oral liquid are combined with a Wnt signal transduction complex in osteoblasts in a targeted mode, and the bone-strengthening and blood-generating oral liquid is obtained; the phosphorylation activity of glycogen synthase kinase-3 is inhibited, so that-catenin enters a nucleus, Runx2 expression is started, and the synthesis rate of the N-terminal propeptide of the type I procollagen is increased; according to the method, a positive anabolism window is established in an original callus formation period of fracture healing by constructing an osteogenesis and osteoclast activity two-way decoupling biological regulation mechanism, so that a positive anabolism effect is achieved, and a positive anabolism effect is achieved. Bone metabolism pathological deviation in an osteoporosis state is corrected, secondary absorption of callus is inhibited while high osteogenic activity is maintained, and biomechanical fracture load of bones after fracture healing is improved.

This disclosure provides methods of preventing or treating cancer in an individual, comprising administering a therapeutic amount of an histone demethylase (LSD1) inhibitor and a therapeutic amount of a glycogen synthase kinase-3 (GSK-3) inhibitor to the individual, and compositions and kits usefule in performing such methods. Also provided are methods of determining the suitability of a cancer patient for treatment with a combination of a histone demethylase (LSD1) inhibitor and a glycogen synthase kinase-3 (GSK-3) inhibitor, and methods of monitoring the efficacy of such treatment.

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.

The invention discloses application of andrographolide and a pharmaceutical composition thereof in preparation of a medicine for preventing and / or treating lung cancer, particularly lung metastatic tumor, and belongs to the technical field of medicine. In-vivo and in-vitro experiments of a system prove that andrographolide can inhibit activation of a nuclear factor kappa B (NF-kappa B) signal channel by down-regulating expression of glycogen synthase kinase 3beta (GSK3beta), and particularly, phosphorylation and nuclear translocation processes of an NF-kappa B p65 subunit Ser536 site are inhibited. According to the effect, transcription and expression of downstream target gene chemotactic factors CCL2 and CXCL1 are effectively reduced, finally, infiltration of tumor-related macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) in tumor tissue is remarkably reduced, aggregation of anti-tumor immune cells such as CD8 + T cells is promoted, an immunosuppressive microenvironment is reversed into an immune activation state, and the immunosuppressive activity of tumor cells is improved. And lung cancer metastasis is inhibited from the source. The invention provides a brand new candidate drug and a clear action mechanism for clinical prevention and treatment of lung cancer metastasis, and has a good development prospect.

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.

Methods for generating lymphatic endothelial cells (LECs) from human induced pluripotent stem cells (hiPSCs) by contacting hiPSCs with a viral vector including polynucleotide sequences encoding ETS2 and / or ETV2, seeding the hiPSCs on a cell culture plate in the presence of a first cell culture media to provide plated hiPSCs, exchanging the first cell culture media for a second cell culture media comprising a glycogen synthase kinase inhibitor and culturing the seeded hiPSCs, replacing the second cell culture media with a third cell culture media including VEGF-A and a TGFβ inhibitor, and inducing expression of the one or more polynucleotide sequences encoding ETS2 and / or ETV2 to provided induced hiPSCs, reseeding the induced hiPSCs on cell culture plates and a fourth cell culture media comprising VEGF-C; and expanding the induced hiPSCs to provide differentiated LEC cells.

Provided herein are compounds of formula (I') or a stereoisomer or tautomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein Y2, Y3, L1, L2, X1, X2, X3, X4, X5, Q1, R1, R2, Rk, Rm, and Rn are as defined elsewhere herein. Also provided herein are methods of preparing compounds of formula (F). 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 discloses a method for inducing and converting mesenchymal cells into neural stem cells, which relates to the technical field of biology and comprises the following steps: (a) providing a group of mesenchymal stem cells cultured in vitro; (b) culturing the mesenchymal stem cells in an induction medium, and inducing the mesenchymal stem cells to differentiate into neural stem cells; wherein the induction medium comprises a basal medium and the following components in effective induction concentrations: a histone deacetylase inhibitor (HDAC inhibitor); a glycogen synthase kinase-3beta inhibitor (GSK-3beta inhibitor); a retinoic acid receptor agonist; the invention provides a set of technical scheme for inducing and transforming the mesenchymal stem cells into the neural stem cells for the first time, which is clear in components, efficient, stable, high in universality and simple and convenient to operate, not only fills the blank in the prior art, but also provides a new cell source and technical support for medical research and clinical treatment of nerve regeneration. The method has an important scientific research value and a wide application prospect.

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 present disclosure provides compounds of Formula (I), and salts, solvates, hydrates, polymorphs, co-crystals, tautomers, stereoisomers, isotopically labeled derivatives, and prodrugs thereof. The provided compounds may be useful for inhibiting kinases, e.g., glycogen synthase kinase 3 (GSK3). The provided compounds may be able to selectively inhibit GSK3a, as compared to GSK3P and / or other kinases. The present disclosure further provides pharmaceutical compositions, kits, and methods of use, each of which involve the compounds. The compounds, pharmaceutical compositions, and kits may be useful for treating diseases associated with aberrant activity of GSK3a (e.g., Fragile X syndrome, attention deficit hyperactivity disorder (ADHD), childhood seizure, intellectual disability, diabetes, acute myeloid leukemia (AML), autism, and psychiatric disorder).

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.

The invention relates to a method for preparing iPSC and differentiating the iPSC into iNKT cells. The method comprises the following steps: (1) introducing a reprogramming induction factor into the iNKT cells, and then reprogramming; (2) culturing the reprogrammed cells to obtain iPSCs, in which the culturing process comprises: (a) culturing the reprogrammed cells in a culture medium comprising basic fibroblast growth factor (bFGF), and (b) culturing the reprogrammed cells in a culture medium comprising an antioxidant, a glycogen synthase kinase 3 (GSK-3) inhibitor, a ROCK inhibitor, and a histone deacetylase (HDAC) inhibitor; and (3) differentiating the iPSCs into the iNKT cells.