102 results about "AMPK" patented technology

The present invention relates to indole and indazole compounds of Formula (I)that activate 5′ adenosine monophosphate-activated protein kinase (AMPK). The invention also encompasses pharmaceutical compositions containing these compounds and methods for treating or preventing diseases, conditions, or disorders ameliorated by activation of AMPK.

The invention relates to a composition that includes a first agent selected from the group consisting of an oxidative phosphorylation inhibitor, an ionophore, and an adenosine 5′-monophosphate-activated protein kinase (AMPK) activator; a second agent that possesses anti-inflammatory activity; and a third agent that possesses serotonin activity.

This disclosure relates to a pharmaceutical composition that includes a first agent selected from the group consisting of an oxidative phosphorylation inhibitor, an ionophore, and an adenosine 5′-monophosphate-activated protein kinase (AMPK) activator; a second agent that possesses anti-inflammatory activity; and a third agent that is a serotonin metabolite.

A biguanide derivative compound with N1-N5 substitution, which is represented by Formula 1, or a pharmaceutically acceptable salt thereof, a method of preparing the same, and a pharmaceutical composition containing the same as an active ingredient are provided. The biguanide derivative may exhibit excellent effect on activation of AMPKα and inhibition of cancer cell proliferation in a low dose, compared to conventional drugs, and thus, may be useful to treat diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovarian syndrome, metabolic syndrome, cancer, etc.

An N1-cyclic amine-N5-substituted phenyl biguanide derivative of Formula 1 or a pharmaceutically acceptable salt thereof, a method of manufacturing the same, and a pharmaceutical composition including the biguanide derivative or the pharmaceutically acceptable salt thereof as an active ingredient are provided. The biguanide derivatives have an effect of inhibiting cancer cell proliferation and also exhibit anticancer activity including inhibition of cancer metastasis and cancer recurrence, because they are effective in activating AMPK, which is associated with the control of energy metabolism, even when administered in a small dose compared with conventional drugs.; Also, the biguanide derivatives are highly effective at lowering blood glucose and lipid concentration by AMPK activation, thus they may be effectively used to treat diabetes mellitus, obesity, hyperlipemia, hypercholesterolemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovary syndrome and metabolic syndrome.

An N1-cyclic amine-N5-substituted phenyl biguanide derivative of Formula 1 or a pharmaceutically acceptable salt thereof, a method of manufacturing the same, and a pharmaceutical composition including the biguanide derivative or the pharmaceutically acceptable salt thereof as an active ingredient are provided. The biguanide derivatives have an effect of inhibiting cancer cell proliferation and also exhibit anticancer activity including inhibition of cancer metastasis and cancer recurrence, because they are effective in activating AMPK, which is associated with the control of energy metabolism, even when administered in a small dose compared with conventional drugs. Also, the biguanide derivatives are highly effective at lowering blood glucose and lipid concentration by AMPK activation, thus they may be effectively used to treat diabetes mellitus, obesity, hyperlipemia, hypercholesterolemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovary syndrome and metabolic syndrome.

An N1-cyclic amine-N5-substituted phenyl biguanide derivative of Formula 1 or a pharmaceutically acceptable salt thereof, a method of manufacturing the same, and a pharmaceutical composition including the biguanide derivative or the pharmaceutically acceptable salt thereof as an active ingredient are provided. The biguanide derivatives have an effect of inhibiting cancer cell proliferation and also exhibit anticancer activity including inhibition of cancer metastasis and cancer recurrence, because they are effective in activating AMPK, which is associated with the control of energy metabolism, even when administered in a small dose compared with conventional drugs. Also, the biguanide derivatives are highly effective at lowering blood glucose and lipid concentration by AMPK activation, thus they may be effectively used to treat diabetes mellitus, obesity, hyperlipemia, hypercholesterolemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovary syndrome and metabolic syndrome.

The present invention relates to provision of AMPK activating agent, endurance enhancing agent, and antifatigue agent, which have rich history of use in foods, high safety, readily available, and high workability, a method of activating AMPK, and a method of preventing, treating and / or ameliorating a life-style-related disease. The present invention provides AMPK activating agent, endurance enhancing agent, and antifatigue agent, each of which contains nootkatone as an active agent. The present invention provides a method of activating AMPK characterized by administering nootkatone in an effective amount, and a method of preventing, treating and / or ameliorating a life-style-related disease characterized by administering nootkatone in an effective amount.

A biguanide derivative compound with N4-N5 substitution, which is represented by Formula 1, or a pharmaceutically acceptable salt thereof, a method of preparing the same, and a pharmaceutical composition containing the same as an active ingredient are provided. The biguanide derivative may exhibit excellent effect on activation of AMPK and inhibition of cancer cell proliferation in a low dose, compared with conventional drugs, and thus, may be useful to treat diabetes mellitus, obesity, hyperlipidemia, hypercholesterolemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovarian syndrome, metabolic syndrome, cancer, etc.

The invention relates to methods for assaying LKB1 activity comprising providing a sample comprising LKB1, contacting the sample with a substrate kinase under conditions that permit phosphorylation, and monitoring incorporation of phosphate into the substrate kinase, wherein the incorporation of phosphate into the substrate kinase indicates LKB1 activity. Preferably the substrate kinase is or is derived from AMPK. The invention also relates to use of AMPK in the treatment or prevention of certain disorders, and to the use of AMPK in the manufacture of medicaments for certain disorders, and to the use of LKB1 in the activation and phosphorylation of AMPK. The invention also embraces yeast cells with certain genetic alterations relating to AMPKK and AMPK.

A N1-cyclic amine-N5-substituted biguanide derivative of Formula 1 or a pharmaceutically acceptable salt thereof, a method of manufacturing the same, and a pharmaceutical composition including the biguanide derivative or the pharmaceutically acceptable salt thereof as an active ingredient are provided. The biguanide derivatives have an effect of inhibiting cancer cell proliferation and also exhibit anticancer activity including inhibition of cancer metastasis and cancer recurrence, because they are effective in activating AMPK, which is associated with the control of energy metabolism, even when administered in a small dose compared with conventional drugs. Also, the biguanide derivatives are highly effective at lowering blood glucose and lipid concentration by AMPK activation, thus they may be effectively used to treat diabetes mellitus, obesity, hyperlipemia, hypercholesterolemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovary syndrome and metabolic syndrome.

The invention encompasses compositions and methods for effectively treating and / or preventing osteoporosis and related disorders such as osteoarthritis and rheumatoid arthritis, and for promoting overall bone and joint health. This is accomplished by totally addressing the multiple mechanisms that lead to such disorders. The invention includes compositions comprising a combination of agents that effectively suppress, regulate or interfere with the various biochemical processes and mechanisms that increase the risk for development of osteoporosis. The present compositions and methods simultaneously promote bone formation and reduce bone resorption by (a) stimulating osteoblast formation and osteogenesis; (b) suppressing adipocyte differentiation; (c) inhibiting osteoclast formation; and (d) increasing apoptosis of osteoclasts. The inventive compositions used for administration to human and other mammalian subjects having or at risk for development of osteoporosis comprise (1) at least one agent capable of modulating expression and / or activity of one or more of peroxisome activated protein receptor gamma (PPAR-γ), CAAT / enhancer binding protein-α (C / EBPα) and Sterol Regulatory Element-Binding Protein (SREBP-1); (2) at least one agent that activates expression and / or activity of one or more of the osteogenic transcription factors (Runx2 / Cbfα1, Dlx5, Osterix, Msx2); (3) at least one agent that activates expression and / or activity of one or more of bone morphogenetic proteins (BMPs: BMP 2 and 4), alkaline phosphatase (ALP), and osteocalcin; (4) at least one agent capable of activating Wnt / β-catenin signaling pathway; (5) at least one agent that inhibits the activity of pro-oxidants including reactive nitrogen species and reactive oxygen species (ROS); (6) at least one agent that suppresses one or more of inflammatory mediators including interleukins IL-1α, IL-1β, IL-6, NF-κB, TNF-α, matrix metalloproteinases (MMPs) and prostaglandin E2 (PGE2); and (7) at least one agent that induces the expression of and / or activates one or more of adenosine monophosphate-activated protein kinase (AMPK), sirtuin (SIRT1) and adiponectin (AP).

The invention relates to the field of drugs, and in particular relates to an AMPK (Adenosine Monophosphate Activated Protein Kinase) activating agent and an application of the AMPK activating agent in preparation of medicaments for treating and / or preventing diabetes mellitus and / or diabetic complication. The invention provides an application of 3H-1, 2-benzodithiole-3-thioketone compound which has a structure shown in a formula I and serves as the AMPK activating agent, and an application of the 3H-1, 2-benzodithiole-3-thioketone compound in preparation of medicaments for treating and / or preventing diabetes mellitus and / or diabetic complication. The compound contains no biguanide group, so that no lactic acidosis occurs once the compound serves as the AMPK activating agent, and higher safety is ensured during the preparation of the medicaments for treating and / or preventing diabetes mellitus and / or diabetic complication.

The invention provides a new function of a compound-pyrocincholic acid 3beta-O-beta-D-quinovopyranosyl-28-O-beta-D-glucopyranoside (PAQG), extracted from metadina trichotoma, in adjustment and control of lipid metabolism in 3T3-L1 cells, and application of the compound in preparation of medicines, food and health care products which are used for relieving obesity and obesity-related metabolic diseases. The PAQG inhibits the differentiation of the 3T3-L1 preadipocytes by activating adenosine monophosphate-activated protein kinase (AMPK), and down-regulates the expression of differentiation-related transcription factors and proteins (PPAR gamma, C / EBP beta, C / EBP alpha and FABP4) and the release of adiponectin. Furthermore, the PAQG inhibits the fat accumulation in the 3T3-L1 mature adipocytes by inhibiting fatty acid synthesis and promoting lipid oxidation. The PAQG relieves the obesity from both fat cell number and fat content under the premise of safe and effective dosage of administration, thus being used for the preparation of medicines, health care products and functional food which are used for preventing and treating the obesity and the obesity-related metabolic diseases.

A N1-cyclic amine-N5-substituted biguanide derivative of Formula 1 or a pharmaceutically acceptable salt thereof, a method of manufacturing the same, and a pharmaceutical composition including the biguanide derivative or the pharmaceutically acceptable salt thereof as an active ingredient are provided. The biguanide derivatives have an effect of inhibiting cancer cell proliferation and also exhibit anticancer activity including inhibition of cancer metastasis and cancer recurrence, because they are effective in activating AMPK, which is associated with the control of energy metabolism, even when administered in a small dose compared with conventional drugs. Also, the biguanide derivatives are highly effective at lowering blood glucose and lipid concentration by AMPK activation, thus they may be effectively used to treat diabetes mellitus, obesity, hyperlipemia, hypercholesterolemia, fatty liver, coronary artery disease, osteoporosis, polycystic ovary syndrome and metabolic syndrome.

A peptide and a peptide complex of the present invention exhibit an anti-obesity effect by inhibiting fat accumulation and decomposing already accumulated fat, and exhibit an excellent effect with respect to diabetes by effectively reducing blood sugar. The peptide and the peptide complex of the present invention decrease the expression of PPARγ, ACC, and aP2, which are adipogenic markers, increase the expression of pHSL, AMPK-α1, CGI-58, and ATGL, which are lipolytic factors, and reduce the size of fat cells and blood cholesterol values. The peptide and the peptide complex of the present invention, which have excellent activity and safety, can be advantageously applied to drugs and quasi-drugs.

The invention discloses a culture medium for culturing neural stem cells on the basis of peripheral blood mononuclear cells. The culture medium comprises components as follows: a DMEM / F12 culture medium and a neurobasal medium in a volume ratio being 1:0.8-1.2 as well as an adenylate cyclase activator, a serum substitute, L-ascorbic acid, an L-glutamine derivative, an ALK inhibitor, a GSK-3 inhibitor, an ALK-2,3,6,AMPK inhibitor and an ALK-4,5,7 inhibitor. The invention further discloses a method for culturing the neural stem cells on the basis of the peripheral blood mononuclear cells. With adoption of the culture medium, the neural stem cells can be obtained from the peripheral blood mononuclear cells as the raw material through directional differentiation culture, materials are taken conveniently and free of quantitative restriction, and moral controversy can be avoided.

The invention encompasses compositions and methods for effectively treating and / or preventing diabetes and / or obesity. This is accomplished by totally addressing the multiple mechanisms that lead to such conditions. The invention includes compositions comprising a combination of agents that effectively suppress, regulate or interfere with the various biochemical processes and mechanisms that lead to diabetes and obesity. The inventive compositions used for administration to human and other mammalian subjects comprise (1) at least one agent capable of modulating expression and / or activity of one or more of peroxisome activated protein receptor gamma (PPAR-γ), CAAT / enhancer binding protein-α (C / EBPα) and Sterol Regulatory Element-Binding Protein (SREBP-1); (2) at least one agent capable of activating Wnt / β-catenin pathway; (3) at least one agent capable of activating the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway; (4) at least one agent that inhibits the activity of pro-oxidants including reactive nitrogen species and reactive oxygen species (ROS); (5) at least one agent that suppresses one or more of inflammatory mediators including interleukins IL-1α, IL-1β, IL-6, NF-κB, TNF-α, matrix metalloproteinases (MMPs) and prostaglandin E2 (PGE2); (6) at least one agent capable of enhancing glucose transporter (GLUT4) and / or inhibiting glucose transporter GLUT2; (7) at least one agent that induces the expression of and / or activates adiponectin and (8) at least one agent that induces the expression of and / or activates sirtuin (SIRT1). The active agents for use herein are natural materials such as phytonutrients, vitamins and minerals. Compositions with combinations of such natural agents have the ability to prevent, reduce or treat diabetes and obesity by (a) clearing glucose and fatty acids from blood, (b) reducing the number of adipose cells and fat storage, (c) interfering with fat, glucose, and cholesterol biosynthesis, and (d) promoting fat and glucose oxidation.Since the present compositions are aimed toward normalizing metabolism and energy expenditure and managing oxidative stress and inflammation, they are also beneficial in relation to physical activity, in particular performance, endurance, fatigue and recovery during intensive and continuous exercise / exertion.

The present invention relates to indole and indazole compounds of Formula (I)that activate 5′ adenosine monophosphate-activated protein kinase (AMPK). The invention also encompasses pharmaceutical compositions containing these compounds and methods for treating or preventing diseases, conditions, or disorders ameliorated by activation of AMPK.

The invention discloses a compound for activating AMPK. The compound is adenine and / or pharmaceutically-acceptable salts thereof. The invention further discloses the application of the compound. The compound is used to activate AMPK (AMP-kinase) and prevent / treat physiological discomfort or diseases. Thus the compound can be applied to prevention and treatment on physiological discomfort or diseases that can be relieved by AMPK for mammals.

The present invention disclosed a medical use of cucurbitane triterpenoids represented by the following formula and isolated from Momordica charantia L. of Cucurbitaceae family in the preparation of medications for prevention and treatment of diabetes and obesity. The above cucurbitane triterpenoids may be acted as a glucose uptake stimulator, an agonist for the translocation of glucose transporter 4(GLUT4) to the cell membrane, and an activator of adenosine monophosphate-activated protein kinase (AMPK). They may have potential for the prevention and treatment of diabetes and obesity.

The invention discloses a composition for promoting meiotic resumption of oocytes of sows and application of the composition. The composition comprises vectors and extracts of ajuga forrestii, oregano, horseradish, cinnamon, rosemary, dunaliella and rhoeo discolor. The composition and the application have the advantages that meiotic resumption of the oocytes of the sows can be promoted, the quality of the oocytes can be improved, the reproductive performance of the sows can be improved, the reproductive lives of the sows can be prolonged, the composition is favorable for activating c-mos and AMPK (adenosine monophosphate activated protein kinase), accordingly, starting of the meiotic resumption of the oocytes of the sows can be promoted, the quality of the oocytes of the sows can be improved, the conception rates and the pregnancy proportions of the sows can be increased, the reproductive health of the sows can be promoted, the immunity and health conditions of the sows can be improved, and the service lives of the sows can be prolonged; the composition can be added into feed for the sows, so that the quantities of eliminated sows among reservation sows and adult sows due to poor oocyte quality of the sows can be greatly reduced, the sow elimination rate can be lowered, and the service lives of high-parity sows can be prolonged; the costs of pig farms can be reduced, and the productivity of the pig farms can be improved.

A topical medication including a therapeutically effective amount of an AMPK (adenosine monophosphate-activated protein kinase) agonist for use in the treatment of one or more the human or animal medical conditions. The medical conditions include, but are not limited to: shingles (herpes zoster), post-herpetic neuralgia (PHN), gout, migraine, trigeminal neuralgia, Complex Regional Pain Syndrome (CRPS), diabetic neuropathy, peripheral neuropathy, rheumatoid arthritis, insect-related wheals, urushiol-related rash, psoriasis, herpes simplex, atopic dermatitis (eczema), contact dermatitis, allergic dermatitis, neurotrophic ulcers, first- and second-degree burns (e.g., sunburn and chemical), fibromyalgia, rubeola, and acne. Also disclosed are a method of employing the composition and a wound dressing incorporating a therapeutically effective amount of an AMPK agonist in combination with an antimicrobial agent.

The invention relates to Vitamin K, its derivatives and combinations to increase the energy levels in diverse disease states and life style disorders, which are characterized by low energy level due to inadequate VO2max, and pO2 and low availability of ATP molecules. VO2max, peak oxygen uptake, is intimately connected to several diseases and life style disorders such as Metabolically Obese but Normal Weight (MONW), Overweight / Obese, diabetes mellitus, coronary artery disease, hypertension, cerebral vascular insufficiency, immune deficient states, cancer, aging-related disorders, reduced cardiopulmonary reserves and muscular fitness in athletics, high altitude climbing and exercise. The invention discloses that innovative blends of components that, in unique combination, synergistically bestow enhancement of VO2max leading to higher energy level, less fatigability and energy adaptations to stressful stimuli in humans and animals. Thus, vitamin K, its derivatives and combinations enhance the energy availability, primarily by the activation of AMP protein kinase (AMPK).

The invention discloses a piperazine compound with AMPK agonist activity, and a preparation method and medical application of the piperazine compound. The piperazine compound is a compound shown as aformula (I) (please see the specifications for the formula), and a pharmaceutically acceptable salt or ester or a prodrug or N-oxide or solvate thereof. The compound can be used for preparing drugs for preventing or treating AMPK-mediated diseases.

The invention discloses an application of kappa-opioid receptor agonists U50 and 488H in preparation of drugs for treating diabetes. In the invention, the good blood sugar reducing effect of kappa-opioid receptor agonists U50 and 488H is creatively discovered, and the research shows that the blood sugar reducing mechanisms of kappa-opioid receptor agonist U50 and 488H are as follows: (1) increasing the level of skeletal muscle adiponectin receptor 1 (AdipoR1) and enhancing the sensitivity of adiponectin and insulin; (2) promoting the membrane translocation of glucose transporter (GLUT4) in skeletal muscle cell and increasing the glucose transport capability of the skeletal muscle cell; and (3) promoting the activation of AMPK (adenosine-monophosphate-activated protein kinase) in the skeletal muscle cell and enhancing insulin sensitivity. In the invention, a new option is provided for the preparation of the drugs for treating diabetes.

A drug includes, RNA interference with protein phosphatase 2Cε (PP2Cε) as an active ingredient. According to the present invention, the activation and deactivation of AMPK can be regulated.

The invention relates to an application of caffeic acid in preparation of drugs for treating hepatic microcirculation disturbance and hepatic injury. Through a series of observation of caffeic acid on hepatic ischemia reperfusion rats, caffeic acid is found to improve the hepatic surface blood flow quantity by the action routes: AMPK[alpha] phosphorylation and PKC[delta] membrane translocation are inhibited, NADPH subunit P41 and P47 membrane translocation is inhibited and NADPH-derived peroxides are inhibited; the activity of a hepatic ischemia reperfusion rat mitochondria respiratory chain is improved, and peroxide production caused by mitochondria injury is reduced, so as to increase the production of ATP; hepatocyte apoptosis caused by ischemia reperfusion is inhibited; and hepatic cell internal cytoskeleton injury caused by ischemia reperfusion is attenuated. The new application in preparation of the drugs for treating hepatic microcirculation disturbance and hepatic injury is provided.

This invention relates to a micromolecular organic compound that is used for activator of human embran mononucleotide activator protein kinase (AMPK). This compound can be used to prevent, postpone or cure diseases that are mediated by AMPK, especial type II diabetes, obesity and tumor. This invention also relates to the preparation of this compound. Otherwise, this invention also relates to application of this compound for activating human embran mononucleotide activator protein kinase or promoting intracellular amylaceum absorbing and application for preparing medicine that cure metabolic disease.

The invention discloses an application of a compound, theacrine, of which the structure is represented as the formula (I), in preparation of a product for promotion of fat burning, blood fat reducing, body fat reducing and fat accumulation reducing. The application of the theacrine is based on that the theacrine can effectively activate activity of SirT3 protease in mitochondria, enhance the functions of key proteins in [beta]-oxidization and oxidative phosphorylation, activate the activity of downstream AMPK inhibiting acetyl coenzyme A carboxylase (ACC), improve metabolism of fatty acid in mitochondria and reduce synthesis of fatty acid, so that the theacrine promotes the fat burning and then achieves the effects of weight losing and fat reducing.