75 results about "MTOR signaling pathway" patented technology

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, R^11a, R^11b, R^11c, and R^11d 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 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.

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 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 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 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 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 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.