29 results about "AMPK" patented technology

The invention discloses a method for promoting skeletal muscle development and application, and belongs to the technical field of biology. The invention provides a method for promoting skeletal muscle development, an AMPK / p38MAPK pathway is regulated and controlled by activating PPARalpha, the way of activating the PPARalpha is to give a PPARalpha agonist GW7647, and the regulation and control of the AMPK / p38MAPK pathway is shown as reduction of AMPK and P38 phosphorylation levels. Experiments show that the expression of MyoD, MyoG and Pax7 in skeletal muscle can be remarkably improved by activating PPARalpha, the phosphorylation level of AMPK and P38 is inhibited, and therefore muscle fiber proliferation and myoblast proliferation are promoted. The technology can be applied to livestock breeding to improve meat yield or develop drugs for treating skeletal muscle atrophy, and has remarkable economic and clinical values.

A method and composition for enhancing adenosine monophosphate-activated protein kinase (AMPK) activity and improving mitochondrial-related oxidative metabolism parameters in motor and sedentary mammals by oral intake of low doses of D-ribose, thereby promoting overall metabolic health in mammals.

Described herein are dosage forms comprising the compound:wherein the dosage form can be a solid dosage form, a liquid dosage form, or a solid amorphous dispersion.

This document provides methods and materials for increasing the level of phosphorylated AMPK. For example, compounds (e.g., organic compounds) having the ability to increase the level of phosphorylated AMPK within cells, formulations containing compounds having the ability to increase the level of phosphorylated AMPK within cells, methods for making compounds having the ability to increase the level of phosphorylated AMPK within cells, methods for making formulations containing compounds having the ability to increase the level of phosphorylated AMPK within cells, methods for increasing the level of phosphorylated AMPK within cells, and methods for treating mammals (e.g., humans) having a condition responsive to an increase in the level of phosphorylated AMPK are provided.

Described herein are compounds of Formula I,wherein the variables are defined herein, their use as activators from AMPK, pharmaceutical compositions containing such compounds and their use to treat, for example, heart failure or peripheral vascular disease.

Compounds having activity as modulators of AMPK are provided. The compounds have Structure (I), (II), (III), or (IV):or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R1a, R2, R3, W, X, Y, R4, R5, R6, X1, X2, X3, n, R8, R9, R10a, R10b, X4, ring A, R11, R12, R13a, R13b, and X5 are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of AMPK are also provided.

This document provides methods and materials for increasing the level of phosphorylated AMPK. For example, compounds (e.g., organic compounds) having the ability to increase the level of phosphorylated AMPK within cells, formulations containing compounds having the ability to increase the level of phosphorylated AMPK within cells, methods for making compounds having the ability to increase the level of phosphorylated AMPK within cells, methods for making formulations containing compounds having the ability to increase the level of phosphorylated AMPK within cells, methods for increasing the level of phosphorylated AMPK within cells, and methods for treating mammals (e.g., humans) having a condition responsive to an increase in the level of phosphorylated AMPK are provided.

The present invention discloses a compound for activating AMPK, which is adenine and / or a pharmaceutically acceptable salt thereof. The invention also discloses the application of the compound, which is suitable for activating AMPK (AMP-activated protein kinase), and using the compound to prevent or treat physiological conditions or diseases, thereby preventing or treating physiological conditions or diseases that can be improved by AMPK in mammals.

The present disclosure relates to compounds of Formula (I):stereoisomers thereof, prodrugs thereof, and pharmaceutically acceptable salts thereof. The present disclosure also relates to uses of the compounds, e.g., to inhibit AMP-Activated protein kinase (AMPK) and treat cancer in a subject.

The invention relates to the technical field of biological medicine, in particular to a serum-free and protein-free culture medium for improving NK cell amplification and killing activity and a preparation method thereof.The serum-free and protein-free culture medium comprises a basic culture medium, an AMPK-HIF1alpha regulating agent, an immunomodulatory factor, a mitochondrial function enhancer, an antioxidant, microelements and a pH buffering agent, the AMPK-HIF1alpha regulating agent is composed of alpha-ketoglutaric acid with the final concentration of 1.4-1.6 mmol / L and AICAR with the final concentration of 0.4-0.6 mmol / L. According to the culture medium, the alpha-ketoglutaric acid and the AICAR are precisely matched to activate an AMPK-HIF1alpha channel, nicotinamide ribose and glutathione are cooperated to optimize a metabolism-antioxidant network, and the industrial problem that amplification and functions cannot be achieved at the same time in serum-free culture of NK cells is solved.

This method and composition involves oral administration of a low dose of D-ribose to enhance adenosine monophosphate-activated protein kinase (AMPK) activity in both exercising and sedentary mammals, improve mitochondrial-related oxidative metabolic parameters, and thereby promote overall metabolic health in mammals.

The present disclosure relates to methods and compositions for editing an AMPK polynucleotide encoding an AMPK protein. The disclosure also relates to methods and compositions for modulating activity of an AMPK protein, for promoting activation of an AMPK protein, for repairing function of a pathogenic AMPK protein, and methods for regulating energy homeostasis and / or for treating or preventing an AMPK-associated disease or condition in a subject.

Disclosed are compounds or pharmaceutically acceptable salts thereof according to formulae IA, IB, or IC as well as pharmaceutical compositions, and methods of use thereof: Formula (IA), (IB), (IC), wherein moieties A and B are further described herein. In certain embodiments, a compound disclosed herein is a 5'-AMP-activated protein kinase ('AMPK') agonist.

The present disclosure relates to the field of biopharmaceuticals, and in particular, to use of lithocholic acid (LCA) as an AMPK activator in pharmaceuticals and a pharmaceutical composition thereof. According to the present disclosure, the LCA is used as a new AMPK activator and can play a role in activating AMPK in various organs or tissues including the liver, kidney, muscle tissue, and the like of mammals, thereby achieving a significant prevention or relieving effect on various indications including high cholesterol, diabetes, and tumors, and providing a thought for developing new drugs and new therapeutic means.

The application belongs to the technical field of bioactive peptides, and discloses application of a polypeptide in regulating lipid metabolism. The polypeptide is IPIQY, and the amino acid sequence is shown as SEQ ID NO. 1. The polypeptide directly acts on hepatocytes to activate AMPK. The application first discloses that the polypeptide IPIQY can directly act on hepatocytes to activate the AMPK signal pathway, and thus realizes reduction of the content of triglyceride in hepatocytes and reduction of lipid accumulation.

The invention discloses a liver cancer prognostic marker and application thereof, relates to the technical field of molecular biomedicine, and discovers that significant correlation exists between mRNA expression quantity increase of a KDM4B gene and overall survival rate reduction of LIHC patients. GO analysis and KEGG analysis are respectively carried out on the co-expression gene of the KDM4B to obtain the correlation between the co-expression gene and signal channels such as cell cycle and AMPK, and the expression of the KDM4B is positively correlated with the immune cell infiltration level. Westernblot shows that the expression of the KDM4B in the liver cancer cell line is higher than that in normal cells. The invention provides a new marker for prognosis of liver cancer, and provides an important basis for selection of an LIHC precise treatment strategy.

This invention discloses the medical use of AMPKγ2 protein for preventing or treating heart failure (HF) after myocardial infarction (MI), belonging to the field of pharmaceutical biotechnology. The expression level of AMPKγ2 protein or its active fragment is correlated with HF caused by abnormal cardiac remodeling due to excessive inflammatory response after MI. MI mice with systemic AMPKγ2 knockout significantly decreased left ventricular systolic function and significantly increased macrophage infiltration; whereas MI mice with systemic AMPKγ2 overexpression showed reduced cardiac dysfunction due to MI and macrophage infiltration. Furthermore, macrophage-specific knockout of AMPKγ2 exacerbated cardiac dysfunction due to MI and macrophage infiltration; conversely, macrophage-specific overexpression of AMPKγ2 alleviated cardiac dysfunction due to MI and macrophage infiltration. This invention provides a new target for the diagnosis and treatment of HF after MI and has significant clinical significance.

The invention belongs to the technical field of medicine application, and particularly relates to a medicine for reversing tumor multidrug resistance. The AMPK signal channel serves as an energy sensing center, and the expression mode of the catalytic subunit PRKAA1 / 2 of the AMPK signal channel has dispute in TNBC. Previous researches show that the AMPK activity in primary breast cancer is generally reduced, and clinical data analysis shows that the AMPK expression of a patient with advanced TNBC is increased and is related to poor prognosis. The invention finds that the expression of PRKAA2 in primary TNBC tissue is reduced, but DOX treatment can induce the expression of PRKAA2, and the expression of PRKAA2 is obviously increased in drug-resistant TNBC cells and TBCSCs. Mechanism research shows that the dynamic expression regulation is derived from CTED2 dependent CBP / p300 mediated H3K27 acetylation modification. The result shows that the AMPK signal has space-time specificity in TNBC, and the function of the AMPK signal may depend on the tumor development stage and the cell subtype.

The present invention relates to synergistic composition for delaying cellular senescence. Particularly, the present invention relates to the bioactive composition for activation of the AMPK-FOXO3a signaling pathway, wherein the composition comprising synergistic combination of FOXO3a promoter and AMPK activators and in specific concentration that controls cell senescence, apoptosis, and autophagy, lire present synergistic composition is useful in controlling vascular ageing disorders.

This invention discloses the application of NT5C1A as a therapeutic target for myocardial ischemia-reperfusion injury, belonging to the field of biomedical technology. Through proteomics screening and in vitro and in vivo experiments, this invention is the first to discover and demonstrate that NT5C1A is upregulated in the pathological process of MIRI, and is a key upstream factor regulating the AMPK / SIRT1 / PGC-1α signaling pathway. Overexpression of NT5C1A can effectively activate this pathway, synergistically regulating multiple downstream pathological processes: promoting the expression of mitochondrial fusion proteins Mfn-2 and OPA1, inhibiting the expression of the splitting protein DRP1; significantly promoting ATP production and improving energy metabolism disorders; and regulating the balance of apoptosis-related protein Bax / Bcl-2 expression, inhibiting cardiomyocyte apoptosis, ultimately reducing myocardial damage, improving myocardial function, and reducing the infarct area. This invention provides a new target and strategy for the precise intervention of MIRI.

The invention discloses a novel application of an AMPK (adenosine monophosphate kinase) activator Aldometanib in preparation of a medicine for inhibiting inflammatory pain. The research finds that animal experiments prove that the AMPK activator Aldometanib can obviously activate p-AMPK, effectively relieve inflammatory pain, improve the pain threshold value and relieve inflammation, and is high in safety, wide in application range and free of obvious side effects. The invention also discloses a molecular mechanism of the Aldometanib for relieving pain, and finds that the Aldometanib reduces the expression of pro-inflammatory cytokines such as TNF-alpha, IL-1beta, IL-6, IL-8 and the like by activating p-AMPK and regulating an STAT3-BDNF-TrkB pathway, and also reduces the activation of microglial cells, thereby reducing the damage and sensitization of nerve cells and playing a role in easing pain. The application of the Aldometanib in the field of medicine is expanded, a safe and effective treatment strategy is provided for treatment of inflammatory pain, and the application has wide clinical application prospects and market value.

Disclosed are activators of the phosphatase PHLPP1 (PH domain and Leucine rich repeat protein phosphatase 1), a widely conserved enzyme involved in the regulation of two signaling networks, mTOR and AMPK, the balance and coordination of which controls the cellular response to either ample or restricted fuel supply to cells. These activators are referred to as SNAP (Snail-derived Activators of PHLPP) compounds as they are based on the structure of a Dormancy Inducing factor (DIF) discovered in hibernating snails. SNAP compounds are demonstrated to increase the activity of both human recombinant PHLPP, and mouse PHLPP1. One such example of a SNAP compound is 3-(2-methyl-8- (2-((oxidanidylsulfonyl)oxy) ethyl)-3,4-dihydro-2H-chromen-2-yl) propanoate-pyridine.

The invention discloses an AMPK agonist and application thereof, and belongs to the technical field of medicinal chemistry, the AMPK agonist simultaneously has anthrone and benzimidazole structures and can be synthesized by taking anthrone compounds, NaH, epichlorohydrin and benzimidazole as raw materials, the synthesis steps are simple and efficient, the AMPK agonist is combined with a beta-regulatory subunit of AMPK to directly activate an AMPK signal channel, and the AMPK agonist can be used for preparing a medicine for treating AMPK. The compound can be used for regulating cell metabolism balance and preventing or treating AMPK-mediated diseases by activating AMPK, particularly can be used for inducing tumor cell apoptosis and inhibiting tumor growth, and has a wide application prospect in the field of tumor treatment.

Compounds having activity as modulators of AMPK are provided. The compounds have Structure (I), (II), (III), or (IV): (I) (II) (III) (IV) or a pharmaceutically acceptable salt, stereoisomer, or tautomer thereof, wherein R1a, R2, R3, W, X, Y, R4, R5, R6, X1, X2, X3, n, R8, R9, R10a, R10b, X4, ring A, R11, R12, R13a, R13b, and X5 are as defined herein. Methods associated with preparation and use of such compounds, pharmaceutical compositions comprising such compounds and methods to modulate the activity of AMPK are also provided.

The invention relates to the field of biological medicine, in particular to application of osteopontin as an AMPK activator, experiments prove that intake of osteopontin cannot inhibit AMPK activity, and AMPK activity can be improved by up-regulating expression of AMPK gamma subunit coding gene Prkag3; in addition, by activating the AMPK gamma subunit coding gene Prkag3, the stability of the tight junction protein can be enhanced by phosphorylating a downstream target Sgk1, so that the effect of repairing the intestinal mucosal barrier function is achieved.

The application discloses a research method of 18beta-glycyrrhetinic acid for liver injury mediated by mitochondrial function damage induced by high-fat diet, which comprises the following steps: S1 test design, S2 test sample collection, S3 index determination, S4 test data statistical analysis, and S5 result. The 18beta-glycyrrhetinic acid (18beta-glycyrrhetinic acid, GA) is first explored to reduce the aggregation of liver collagen fibers by down-regulating the TGFbeta1-Smad2 / 3 signal, thereby relieving liver fibrosis, and improving the liver injury of largemouth bass caused by high-fat diet (HF). Secondly, the GA can reduce the expression of calcium ion transport proteins in the endoplasmic reticulum and mitochondria by activating the Ampk-Pgc1alpha-Sirt3 signal pathway, relieve liver mitochondrial damage, reduce the content of ROS, thereby inhibit the activation of pro-fibrotic factors. The HF can up-regulate the activity of liver function-related enzymes of largemouth bass, increase the deposition of liver lipid droplets, and the aggregation of collagen. After adding the GA, the adverse effects caused by the HF can be obviously improved, thereby relieving the liver injury of largemouth bass induced by the HF.

The present invention relates to adenine which is useful to activate AMP-activated protein kinase (AMPK) and the use of adenine in the prevention or treatment of conditions or disease and thereby prevent or treat conditions or diseases which can be ameliorated by AMPK in a mammal.

The invention relates to the technical field of biological medicines, in particular to a method for regulating oxidative stress of ischemic injury by GDF-15 based on an AMPK (adenosine monophosphate kinase) signal pathway, which comprises the following steps: culturing AC16 myocardial cells, treating primary myocardial cells, and carrying out hypoxia experiment and function and molecule detection; carrying out quantitative analysis on fluorescence signals according to the obtained fluorescence image, and determining expression modes of GDF-15 and HI F-1alpha in the MI heart tissue; detecting the protein level of the GDF-15 in the MI heart tissue, verifying the expression mode of the GDF-15, or adjusting dyeing parameters; carrying out statistical analysis on the detection parameters, and determining a specific parameter group with significant differences among the parameters; determining a GDF-15 regulation pathway, and judging a production mode of ROS in AC16 myocardial cells and a phosphorylation state of an AMPK signal pathway; and carrying out exogenous drug delivery immunofluorescence analysis, and judging the expression relationship between the GDF-15 and the HI F-1alpha. According to the invention, a new insight is provided for the cardiac protection effect of the GDF-15 and the potential of the GDF-15 as a myocardial infarction treatment target by illuminating the molecular mechanism of the GDF-15.

The invention discloses application of an AMPK / mTOR signal channel activator in preparation of a medicine for preventing and / or treating heart failure, and belongs to the technical field of biological medicine. In order to solve the problem that whether the heart function improvement of the body resistance strengthening and heart nourishing formula is related to the influence of AMPK / mTOR pathway regulation on autophagy related protein expression is not clear yet, an HFrEF rat model is constructed, and experiments verify that the body resistance strengthening and heart nourishing formula activates an AMPK / mTOR signaling pathway, down-regulates the p62 expression of autophagy protein, up-regulates the expressions of Becline1, LC3I and LC3II, relieves the pathological damage and fibrosis degree of myocardial tissue, and has the effect of strengthening the heart function. Therefore, the treatment effect of HFrEF is achieved. Experimental results show that the AMPK / mTOR signal channel can be used as a therapeutic target of the HFrEF, and the effect of treating the HFrEF is achieved by activating the AMPK / mTOR signal channel, so that a theoretical basis is provided for further clinical development of HFrEF therapeutic drugs and application of AMPK / mTOR signal channel activators.