75 results about "MTOR signaling pathway" patented technology

The present invention relates to novel methods for the prevention, treatment and diagnosis of Alzheimer's disease. In addition, the invention relates to methods for assessing an individual's susceptibility or pre-disposition to Alzheimer's disease. The methods of the present invention involve the use of therapeutic targets and diagnostic and / or predictive markers within the mTOR signalling pathway. The methods also involve screening subjects for genetic polymorphisms associated with rapamycin-sensitive genes.

The invention discloses a purpose of a polyether compound in medicine preparation and an anti-tumor medicine screening method. The medicine is used for regulating and controlling at least one of the following signal channels: a calcium ion signal channel, a Wnt signal channel, a Hippo signal channel, a TNF signal channel, a VEGF signal channel, a p53 signal channel, an NF-kappa B signal channel, an Ras signal channel, an mTOR signal channel, an RNA degradation signal channel, a PPAR signal channel, a cAMP signal channel, an HIF-1 signal channel, an Insulin signal channel, an AMPK signal channel, an Rap1 signal channel, an apoptosis signal channel, a cell cycle signal channel, a cGMP-PKG signal channel, a DNA copying signal channel, an MAPK signal channel, a PI3K-Akt signal channel and an autophagy signal channel. The polyether compound provided by the invention can cause the tumor cell death through regulating and controlling various signal channels; and a better anti-cancer effect isachieved.

The present invention provides methods, compositions, and combinations for treating cancer via combined use of a compound of formula (I), and / or their subgenra, or a pharmaceutically acceptable salt, tautomer or stereoisomer thereof, wherein R1, R2, R3, R8, R9, R11a, R11b, R11c, and R11d are as defined herein, and at least one therapeutically active agents selected from inhibitors of PI3K / AKT / mTOR pathway, active agents associated with the treatment of prostate cancer, and anticancer agents.

The invention discloses a thiophene and pyridine compound as well as a preparation method and application thereof. The thiophene and pyridine compound as well as the preparation method and the application thereof have the benefits that the synthesis of the thiophene and pyridine compound with a novel structure and the application of the thiophene and pyridine compound to anti-cancer are provided; as a PI3K-Akt / mTOR signal path plays an important role in the occurrence and the development of tumors and has close occurrence and development relations with a breast cancer, a gastric cancer, a colon cancer, a rectal cancer, an ovarian cancer, a prostatic cancer and other tumors, when the PI3K-Akt / mTOR signal path is abnormal, the cancers may be caused; the thiophene and pyridine compound disclosed by the invention can restrain the abnormity of the PI3K-Akt / mTOR signal path, so as to achieve the purposes of preventing and treating the cancers. The thiophene and pyridine compound disclosed by the invention not only provides a new strategy and a new idea for tumor treatment, but also provides a new direction and a new idea for the research and development of anti-tumor drug.

The invention relates to the application of thalazozolopyrimidine compounds in the preparation of drugs for treating lung cancer. The invention also provides the application of the thalazozolopyrimidine compound in the preparation of medicines for treating malignant melanoma and human ovarian cancer. The advantage of the present invention is that: as a MNK1 inhibitor, the thalazozolopyrimidine compound of the present invention is a new target for the treatment of lung cancer and inhibits two mechanism pathways of lung cancer pathogenesis, MAPK and mTOR signaling pathways, rather than targeting a single mechanism, so as to avoid and reduce drug resistance; in view of the current poor therapeutic effect and low survival rate of lung cancer and malignant melanoma, it can greatly improve the therapeutic effect of these two diseases, which has great positive significance to the society; the present invention has huge economic benefits .

The invention provides application of a DNA tetrahedron to induction of autophagy. The DNA tetrahedron is synthesized from four single DNA strands through self-assembling, wherein the sequences of thefour single DNA strands are shown in SEQ ID No. 1-4. The DNA tetrahedron can activate a PI3K / AKT / mTOR signaling pathway so as to conduct induction effect on autophagy. Specifically, the DNA tetrahedron can act on the upstream protein AKT of mTOR and conducts inhibition effect on the expression of the protein mTOR by activating the expression of AKT; meanwhile, DNA tetrahedron can negatively act on mTOR by up-regulating the expression of the upstream protein PI3K of mTOR so as to allow the expression of mTOR to be inhibited, so autophagy is further induced and biomolecules in cells are highlyrecycled for the cells, and thus, the proliferation and migration of cells are improved.

The invention belongs to the technical field of functional analysis methods of disease metabolism biomarkers, and provides a biomarker metabolic pathway and an analysis method. The metabolic biomarker is stearic acid, phytosphingosine, glycine, glutamine and phospholipids; an acting target spot of the metabolic biomarker is a target protein related to a depression nervous system, immune response and endocrine; and the metabolic pathway is a PI3K-Akt signaling pathway, an mTOR signaling pathway, an MAPK signaling pathway, an erbB signaling pathway, a neurenergen signaling pathway, an Rap1 signaling pathway and an Ras signaling pathway. A functional network analysis method suitable for depression characteristics is established, and the clinical application of these biomarkers helps to optimize the diagnosis of depression, and can provide some valuable clues for the subsequent depression network function researches.

The invention discloses a small-molecule compound composition capable of efficiently inducing differentiation of human multipotent stem cells into myocardial cells. Specifically, the small-molecule compound composition provided by the invention comprises (i) a mTOR signal pathway inhibitor, (ii) a Wnt pathway promoter and (iii) an optional pharmaceutically-acceptable vector. The small-molecule compound composition provided by the invention can efficiently induce differentiation of multipotent stem cells into myocardial cells, wherein the differentiation rate of myocardial cells is as high as 86% after primary screening, and the differentiation rate of myocardial cells is as high as 98.3% after optimization.

The invention concerns carbon dioxide extracts of Curcuma amada (mango ginger), including supercritical carbon dioxide extracts of C. amada; methods for their production; compositions comprising the extracts; methods for treating or delaying the onset of conditions such as cell proliferation disorder (e.g., cancer), inflammation, infection, hyperlipidemia, hypercholesterolemia, hypertriglyceridemia, hyperglycemia, platelet hyper-aggregation, immune disorder such as autoimmune disorder, or neurodegenerative condition; and methods for inhibiting expression of Bcl-2, Bak, and p53 genes; inhibiting expression of the COX-2 and NF-kB genes, inhibiting production of phosphorylated target of rapamycin (TOR), modulating AMP-activated protein kinase (AMPK), inhibiting protein kinase B (AKT) signaling, modulating the Ras / Raf / MEK / ERK signaling pathway, and modulating the Ras / PI3K / PTEN / Akt / mTOR signaling pathway. Another aspect of the invention concerns a method for inhibiting contamination, comprising applying the extract or composition of the invention to a surface. Another aspect of the invention concerns a method for promoting longevity of a cell in vitro or in vivo, comprising contacting a target cell in vitro or in vivo with an effective amount of the extract or composition of the invention. Another aspect of the invention concerns a method for promoting longevity of a subject, comprising administering an effective amount of the extract or composition of the invention. Another aspect of the invention concerns a method for inhibiting the metabolism of a cancer cell, comprising contacting the target cancer cell in vitro or in vivo with an effective amount of the extract or composition of the invention. Another aspect of the invention concerns a kit including the extract or composition; a container containing the extract or composition; and packaging material.

The invention discloses emodin as an inhibitor of activated molecules p-Akt and p-mTOR of a PI3K / Akt / mTOR signal transduction pathway and application thereof, wherein the emodin is a purely natural anthraquinone monomer compound extracted from rhubarb as a Chinese traditional medicine and has multiple biologic activities such as anti-microbes, anti-inflammation, antioxidation, immune regulation, liver protection and the like. The invention finds that after acute leukemia multidrug-resistance cells HL-60 / ADR, acute promyelocytic leukemia retinoic acid drug-resistant cells MR2 as well as corresponding sensitive cells NB4 and acute leukemia primary cells are acted by the rhubarb, key signal activated molecules of the PI3K / Akt / mTOR signal transduction pathway, particularly p-Akt and p-mTOR, are inhabited with specificity; in vivo researches verify that after the emodin is dosed, all the key activated molecules p-Akt, p-p65 and p-mTOR of the PI3K / Akt / mTOR signal pathway in acute leukemia nude mouse transplanted tumor tissue protein are expressed and downwards regulated, which indicates that the emodin can be used as a novel targeting inhibitor for PI3K / Akt / mTOR signal transduction activated molecules, particularly p-Akt and p-mTOR, and is applied to treating malignant tumors of a blood system.

The invention relates to a preparation method and application of tolerogenic dendritic cells capable of keeping stability in the inflammatory environment. The preparation method is characterized by using a monomer structure compound for carrying out targeted inhibition on phosphorylation of mTOR signal channel protein, and carrying out in-vitro tolerance short-time induction and culture of human dendritic cells. The result shows that the prepared tDC still maintains a stable tolerance regulation function when the tDC is irritated by inflammatory molecules. A new tDC preparation method is builtand is capable of ensuring the survival rate of cell products in moderate concentration and time and preparing tDC cell products which can still stably maintain the tolerance function in the inflammatory environment; the raw materials adopted by the preparation method easily pass GMP authentication; the preparation process is simple, convenient and economical; the prepared products are stable andeffective and are easily standardized; the prepared tDC can be applied to adoptive infusion, can be used for treating multiple allergic immune reactive diseases, and has great potential in clinical application.

Methods and composition for tumor therapy, especially esophageal adenocarcinoma (EAC), are described. For example, in certain aspects methods for determining Hedgehog and mTOR signaling pathway status to select patients for administering a combination therapy of Hedgehog and mTOR signaling inhibitors are described. Furthermore, the invention provides compositions that involve testing kits for determining signaling status.

Methods are provided for stimulating ovarian follicles in a mammal through activation of the mTor signaling pathway.

The invention discloses a medicine that cures muscle atrophy after spinal cord injury and its application method: the medicine that cures muscle atrophy after spinal cord injury is losartan. The application method is that losartan activates a signal pathway of IGF1 / Akt / mTOR and inhibits an expression of MuRF-1; A receptor blocking pharmacon of angiotensin II takes effect through activating the pathway of IGF-1 / Art / mTOR and inhibiting a ubiquotin-proteasomes system. The receptor blocking pharmacon of angiotensin II can improve the skeletal muscle atrophy after spinal cord injury of rats and may take effect through activating the pathway of IGF-1 / Akt / mTOR and inhibiting the ubiquitin-proteasomes system, which provides a part of basis for later clinical application and combined therapy.

The invention discloses application of miR-130a to diagnosis, treatment and prognosis of ovarian cancer. The miR-130a is defined, through in-vivo and in-vitro function test, that an mTOR (mammalian Target of Rapamycin) signal path is over-expressed through inhibiting translation of TSC1mRNA (Tuberous Sclerosis 1 Messenger RNA (Ribonucleic Acid)) by the miR-130a, so that proliferation and invasion of ovarian cancer cells are promoted and autophagy of the cells is inhibited. The data testifies that the miR-130a with a reduced endogenous property can be used for inhibiting malignant biological behaviors including growth, invasion and the like of ovarian cancer tumors. Based on the characteristics, a specific miR-130a inhibitor can be designed, the content of TSC1 in a body is recovered and the mTOR signal path is inhibited, so that the aim of treating the ovarian cancer is realized.

The invention discloses a feed additive for promoting growth of porcine skeletal muscle and application thereof in the technical fields of feed processing and fish breeding and poultry raising. The feed additive is a carnosine obtained from condensation of beta-alanine and L-histidine with a relative molecular weight of 226.24, and is a natural antioxidant. The feed additive is capable of activating an mTOR signal pathway and enhancing proliferation of porcine skeletal muscle satellite cells, thus promoting the growth of the porcine skeletal muscle. The mechanism of porcine muscle growth is explained in terms of cells and an important idea is offered for development of animal growth promoting additives. When the additive is added to a pig feed, the growth performance of pigs and the meat producing efficiency can be improved. The additive has remarkable economic benefits, is safe without any risk even in long-term use, and has the characteristics of going green, safety, and environmental protection.

The invention discloses application of PD149163 to preparation of medicine for treating cerebral arterial thrombosis. According to application of PD149163 to preparation of the medicine for treating cerebral arterial thrombosis, on the premise that cerebral blood flow of a focal zone is not affected in the cerebra ischemic reperfusion process, PD149163 plays a protective role in rat cerebral injury at the acute stage caused by focal cerebra ischemic reperfusion. PD149163 possibly resists to nerve cell apoptosis caused at the acute stage of cerebra ischemic reperfusion by blocking an AMPK-mTOR signal channel and inhibiting autophagy.

The invention discloses application of a mTOR signal path inhibitor to preparation of a medicament for preventing or treating extragenetic hearing impairment. The mTOR signal path inhibitor is selected from at least one of sirolimus, sirolimus analogue and second-generation mTOR signal path inhibitor; the sirolimus analogue is selected from at least one of everolimus, temsirolimus and Deforolimus;the second-generation mTOR signal path inhibitor is selected from at least one of PI3K / mTOR double inhibitor, selective mTORC1 / 2 inhibitor and ATP competitive mTOR kinase inhibitor. As found by the inventor of the application, the mTOR signal path inhibitor can effectively relieve damage to inner ear hair cells and spiral ganglion cells caused by non-genetic factors such as ototoxic drug, remarkably improve the impaired listening ability, and effectively prevent and treat extragenetic hearing impairment.

The invention relates to an application of 5-methyl-dihydrobenzofuran-imidazole salts in preparation of PI3K kinase inhibitors, mTOR signaling pathway inhibitors and tumor prevention and treatment drugs. Compounds with 3-(2-bromobenzyl)-1-((2,3-dihydrobenzofuran-5-yl)methyl)-5,6-dimethyl-1H-benzo[d]imidazol-3-ium bromide(B591) as a representative can target to PI3K kinase to inhibit an mTOR signaling pathway and inhibit tumor growth. More importantly, compared with normal tumor cells, B591 more significantly inhibits tumor stem cells and effectively prevents breast cancer cell metastasis and recurrence of breast cancer after treatment with a chemotherapeutic drug paclitaxel. The compounds have the advantages of strong pharmacological activity, clear action mechanism, safety, low toxicity and good stability, can be used as novel drugs, health care products and / or dietary additives, are used for preparing anti-tumor drugs, provide a new choice for the field of tumor treatment and have great application value, and can also be used as chemical tool molecules for research on the PI3K / Akt / mTOR signaling pathways.

The present invention belongs to the field of pharmaceutical Chemistry. In particular, the present invention relates to a pyridopyrimidine or pyrimidopyrimidine compound as represented by general formula (I), or an isomer thereof or a pharmaceutically acceptable salt, ester, prodrug or solvate thereof, a preparation method, a pharmaceutical composition and uses thereof in preparing a mTOR inhibitor. As a mTOR inhibitor, the compound or the pharmaceutical composition thereof can be used for treating a disease or condition due to PI3K-AKT-mTOR signalling pathway malfunction.

The invention discloses a natural small molecular compound and its application in the preparation of antitumor drugs. The small molecular compound is isolated from the fruiting body of Albatrellus confluens, and has a new type of C-skeleton composed of a pyrane-type sesquiterpene-like structure as a side chain connected with resorcinol, named Neoalbaconol. A series of studies have found that Neoalbaconol inhibits tumor cell proliferation and induces tumor cell apoptosis by inhibiting NF-κB, E2F-1 and PI3K / AKT / TSC2 / mTOR signaling pathways. It has significant broad-spectrum anti-tumor activity and can be used to prepare antineoplastic drugs.

The invention belongs to the field of pharmaceutical and chemical industries and relates to a compound as shown in a general formula I, a pharmaceutical salt or a hydrate of the compound, a preparation method of the compound as shown in the general formula I, a pharmaceutical composition containing the compound as shown in the general formula I or the pharmaceutical salt or the hydrate of the compound and an application of the compound as shown in the general formula I or the pharmaceutical salt or the hydrate of the compound in production of drugs, wherein the compound as shown in the generalformula I has an effect on inhibiting a PI3K / Akt / mTOR signal pathway of a mammal, all substituent groups in the general formula I are defined as the specification, and the drugs are used for treatingdiseases caused by abnormal expression of the PI3K / Akt / mTOR signal pathway of the mammal.

The invention discloses application of 4-[6-(4-isopropoxypheny) pyrazolo [1, 5-a] pyrimidin-3-yl] quinoline to preparation of autophagy inhibitors or tumor sensitizing drugs, belonging to the field of biomedicine. According to researches, the 4-[6-(4-isopropoxypheny) pyrazolo [1, 5-a] pyrimidin-3-yl] quinoline can inhibit autophagy induced by hunger, AICAR (5-Aminoimidazole-4-carboxamide 1-beta-D-ribofuranoside) and rapamycin by activating an Akt-mTOR signal pathway. According to further researches, the 4-[6-(4-isopropoxypheny) pyrazolo [1, 5-a] pyrimidin-3-yl] quinoline can enhance the breast cancer cell resisting effect of tamoxifen. Therefore, the application of 4-[6-(4-isopropoxypheny) pyrazolo [1, 5-a] pyrimidin-3-yl] quinoline disclosed by the invention has wide application prospect in preparation of autophagy inhibitors or tumor sensitizing drugs.

The invention provides application of N-hydroxyphthalimide compounds or pharmaceutically-acceptable salt of N-hydroxyphthalimide compounds in preparation of mTOR signal path inhibitor, and application in preparation of anti-tumor medicine. It is proved that compounds N-hydroxyphthalimide (NHPI) can restrain mTOR signal paths, tumor cell proliferation can be restrained, tumor cell apoptosis can be induced, growth of breast cancer tumor transplanted subcutaneously in nude mice can be restrained, and the good in-vivo and in-vitro anti-tumor effect is displayed. The compounds are used for preparing anti-tumor medicine, a good choice is provided for the field of tumor treatment, and quite high application value is achieved.

The invention belongs to the field of anti-tumor drugs, and particularly relates to a preparation method and application of a zinc organic framework drug-loading system entrapping rapamycin. A following solution is put forward currently, specifically, the preparation method comprises the following steps: 1, zinc nitrate is dissolved in methanol, and the rapamycin is added into a zinc nitrate hexahydrate solution; 2, after mixing and stirring for 5 min, a 2-methylimidazole solution is dropwise added, then stirring is conducted for 15 min, and centrifuging for collection is conducted; and 3, washing is conducted with a mixture of H2O and methanol for three times, and after washing, solid nanoparticles are obtained through vacuum drying. The rapamycin is taken as a raw material to prepare thezinc organic framework drug-loading system entrapping the rapamycin, the zinc organic framework drug-loading system can be uniformly dispersed in water under the ultrasonic condition to prepare an intravenous injection preparation, the reagent can cooperatively conduct autophagy induction and inhibit an mTOR signal pathway to enable MCF-7 / ADR to restore sensitivity to chemotherapy, cancer of certain tissue or a certain organ can be treated or relieved, and obvious killing and inhibiting effects on tumor cells are achieved.

The invention discloses application of a compound to the preparation of an mTOR inhibitor, belongs to the field of medicine, and in particular relates to the application of a compound SC06 to the preparation of the mTOR inhibitor. The compound has the functions of inhibiting an mTOR signal channel so as to induce apoptosis of tumors and inhibiting tumor growth. The compound SC06 can inhibit the proliferation and growth of tumor cells and can effectively induce the apoptosis of tumor cells, therefore showing a therapeutic action on tumors.

The invention provides establishment and application of an H-ras 12V transgenic male mouse liver tumor cell line MMHRL1. Specifically, the H-ras 12V transgenic male mouse liver tumor cell line MMHRL1 provided by the invention has stable properties, can be stably passed for a plurality of times, is applicable to establishment of a liver tumor animal model and is an ideal cell line for foundation and clinical prophase application researches of liver tumor. Furthermore, the H-ras 12V transgenic male mouse liver tumor cell line MMHRL1 can be used for expressing H-ras mutated cancer genes and has highly-activated Ras / MAPK (Renin-angiotensin system / Mitogen-activated Protein Kinase) and PI3K / AKT / mTOR (Phosphoinositide 3-kinase / protein kinase B / mammalian Target of Rapamycin) signal paths. The invention further provides the application of the cell line to the aspects of establishment of model animals, drug screening and the like.

The invention relates to the technical field of medicines, in particular to an application of adenosine and an autophagy inhibitor in the preparation of drugs for treating the colon cancer. The application has the advantage that the application firstly finds that the adenosine induces autophagy by inhibiting a PI3K / Akt / mTOR signaling pathway in colon cancer cells; from the order of phenotype, adenosine-induced apoptosis precedes the autophagy. Lowering of autophagy-related gene expression can promote the proportion of the adenosine-induced apoptosis in colon cancer cells, so the adenosine combined with the autophagy inhibitor (like chloroquine or 3-methyladenine) can kill the colon cancer cells more completely and achieve better clinical treatment effects.

Compounds and their use in modulating the Ras / Raf / MEK / ERK and PI3K / Akt / mTOR signaling pathways to protect normal cells in scenarios such as chemotherapy to kill cancer cells are provided. The compounds inhibit phosphatidylinositol 5-phosphate 4-kinase (PI5P4K) and / or increase phosphoinositide 3-kinase-interacting protein 1 (PIK31P1). Also provided are methods for identifying such compounds, methods of treatment using same and other uses.