41 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.

A method of treating cancer in a pediatric patient in need thereof comprises administering to the patient 9-ING-41 in combination with an additional therapeutic agent.

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 relates to the technical field of biological detection, in particular to a primer probe group, a detection reagent and a detection kit for detecting glycogen synthase kinase 3 genes. The primer probe group of the GSK-3beta gene provided by the invention is high in specificity, the amplification performance of the detection reagent is excellent, the kit provided by the invention has the advantages of high specificity, high sensitivity and high accuracy when being used for rapidly identifying GSK-3beta in a kidney lesion tissue sample or urine, the stable detection lower limit is 0.05 ng / mu L, and the kit can be used for rapidly identifying the GSK-3beta in the kidney lesion tissue sample or urine. In addition, interference of other types of common pathogens on experimental results can be avoided, and a reliable experimental basis is provided for GSK-3beta identification.

The invention provides a culture medium for NK cell culture and a preparation method of NK cells. The culture medium comprises a coating solution, an activation culture medium and a proliferation culture medium, the coating solution comprises an antibody, recombinant human fibronectin and a buffer solution; the activation culture medium comprises a first cell factor, a glycogen synthase kinase inhibitor and an NK basal culture medium; the proliferation culture medium comprises a second cell factor and an NK basal culture medium. The problem that in the prior art, prepared NK cells are poor in quality can be solved, and the method is suitable for the field of cell culture.

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 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.

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

Provided herein is a method of treating a cancer in a subject in need thereof, said method comprising administering a pharmaceutical composition comprising a glycogen synthase kinase-3 beta (GSK3-β) inhibitor and a histone deacetylase (HDAC) inhibitor, wherein said cancer comprises an increased amount or expression of a GATA gene, a keratin 17 (KRT17) gene, a TP56 gene, a CYP3A gene, or a combination thereof.

The invention discloses application of a glycogen synthase kinase GSK3 inhibitor composition in prevention and treatment of leukemia, and belongs to the technical field of medicines. The glycogen synthase kinase GSK3 inhibitor composition is prepared from CHIR99021, SB216763 and LY2090314, and can be used for preparing the glycogen synthase kinase GSK3 inhibitor composition. The invention discloses that the glycogen synthase kinase GSK3 inhibitors CHIR99021, SB216763 and LY2090314 have a synergistic effect in the aspect of treating the leukemia, a foundation is laid for researching the action mechanism of the glycogen synthase kinase GSK3 inhibitors in treating the leukemia, and a technical support is provided for further developing leukemia treatment medicines.

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 plant genetic engineering, in particular to a rape glycogen synthase kinase 3beta-291 mutant and application thereof. The BnbgrT291I is subjected to overexpression and fixed-point editing in the brassica napus, a transgenic plant with the dwarfing and branching angles obviously reduced and the pod density obviously increased is obtained, an important theoretical basis and precious germplasm resources are provided for improvement of the brassica napus plant type, and the BnbgrT291I gene has a wide application prospect.

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.

The present disclosure relates to compositions and methods of suppressing or inhibiting Glycogen Synthase Kinase 3 (GSK-3) and / or β-catenin (beta-catenin). In some aspects, inhibition of GSK-3 and / or β-catenin treats, prevents, or ameliorates a GSK-3 or β-catenin related disease in a subject. In some aspects, provided herein is a method of identifying synergistic modulation of GSK-3.

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 relates to the technical field of plant genetic engineering, in particular to a rape glycogen synthase kinase 3beta-293 mutant and application thereof. It is found that when the rape green revolution gene BnbgrE293 site is mutated into F, H, N, C, G, M, Q, R, V, I, L, Y and W, dwarfed plants can be obtained, and the method plays an important role in rape plant type improvement. Wherein when the BnbgrE293 site is mutated into F, H, R, V, I, L, Y and W, plants which are semi-dwarf, obviously reduced in branching angle and obviously increased in silique density can be obtained. The invention provides an important theoretical basis and valuable germplasm resources for improving the plant type of the brassica napus.

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.

Provided are compounds, methods, and pharmaceutical compositions for reducing the amount or activity of GYS1 RNA in a cell or subject, and in certain instances reducing the amount of GYS1 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.

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.

The invention relates to the technical field of biological medicines, in particular to a method for inducing neural stem cells to differentiate into dopaminergic neurons by a small molecule compound. A magnetic mesoporous silica-phase change liposome composite system is constructed, wherein the surface of a three-dimensional porous bioglass substrate is modified with bifunctional peptide, and a glycogen synthase kinase inhibitor, a transmembrane protease inhibitor and a bone morphogenetic protein receptor antagonist are loaded on the three-dimensional porous bioglass substrate. A response mechanism of a photosensitive cyclic adenylate analogue and a dopamine synthesis precursor is activated through blue light pulses, and finally targeted sorting is completed by a fluorescent tracing substrate, so that a high-purity functional dopaminergic neuron population is obtained. Through physical microenvironment optimization, chemical signal channel regulation and control and multi-dimensional integration of a light-operated maturation mechanism, efficient and controllable differentiation of neural stem cells to dopaminergic neurons is realized, and a standardized preparation scheme is provided for Parkinson's disease cell therapy.