42 results about "Erk signaling" patented technology

Provided is a method of treating or preventing a cardiomyopathy associated with activation of at least one kinase in the MAP kinase signaling pathway in heart tissue by providing to a subject an inhibitor of at least one kinase in the ERK signaling pathway or in the JNK signaling pathway, or both. In some embodiments, the cardiomyopathy is associated with one or more mutations in the LMNA gene, which encodes A-type nuclear lamins, or in the EMD gene, which encodes an inner nuclear membrane protein.

The invention consists in that substances acting as cascade inhibitors of the Raf / MEK / ERK signaling path-way, in particular MEK inhibitors, are used for the production of a drug for the preventive and antiviral therapy against DNA and RNA viruses, in particular against intranuclear-replicating negative strand RNA viruses, for instance influenza or Borna disease viruses.

The invention provides pyrrolidino-substituted 1,4-naphthoquinone derivatives that modulate the activity of protein kinases, and it relates to the use of the derivatives in pharmaceutical compositions for treating cardiovascular disorders and malignancies. The invention particularly provides medicaments for treating disorders associated with MAPKs signaling, ERKs signaling, p38 signaling, and JNKs signaling.

The invention relates to an antitumor polypeptide for targeted inhibition on an ERK signal channel and application of the antitumor polypeptide. According to the antitumor polypeptide, a micro-molecule polypeptide for targeted inhibition on the ERK signal channel is established; a series of biological experiment shows that the micro-molecule polypeptide is capable of effectively inhibiting drug resistance of a PI3K / AKT inhibitor or a paclitaxel medicine in the antitumor treatment process for multiple tumors such as prostate cancer, breast cancer, colon cancer and rectal cancer, and has a remarkable synergic antitumor function; as the ERK signal channel exists in multiple tumors and is one of important signal channels for promoting cell growth and tumor generation and development, the micro-molecule polypeptide can be used for treating the tumors, and preferably the micro-molecule polypeptide is used together with the PI3K / AKT inhibitor or the paclitaxel medicine.

The invention provides methods, therapeutics and kits for treating and preventing diseases or conditions associated with excessive lipolysis, in particular TNF-α induced lipolysis, and / or excessive free fatty acid levels. Exemplary conditions include insulin-resistance, diabetes, in particular NIDDM, obesity, glucose intolerance, hyperinsulinemia, polycystic ovary syndrome, and coronary artery disease. In a preferred embodiment, the method includes administering to a subject in need a pharmaceutically effective amount of an inhibitor of the JNK signal transduction pathway and / or an inhibitor of the MAPK / ERK signal transduction pathway.

The invention relates to a sorafenib tosylate-hydroxypropyl-beta-cyclodextrin clathrate compound and a preparation method thereof. Sorafenib plays the role of anticancer by inhibiting RAS / RAF / MEK (methyl ethyl ketone) / ERK (extracellular signal-regulated kinase) signal conducting channels and inhibiting tumor angiogenesis, and is directed to cancer cells instead of normal cells. The sorafenib is almost insoluble in water, and the average relative bioavailability of oral administration is 38% to 49%. According to the preparation method of the invention, the sorafenib tosylate-hydroxypropyl-beta-cyclodextrin clathrate compound is prepared based on the clathrate compound-forming property of hydroxypropyl-beta-cyclodextrin, thereby increasing medicine dissolvability, improving medicine dissolution and raising medicine bioavailability.

The present invention is a method of creating a population of hemogenic endothelial cells with arterial specification and enhanced T cell potential. In one embodiment, the method uses ETS transgene induction at the mesodermal stage of differentiation. In another embodiment, the method activates ERK and NOTCH signaling at the mesodermal stage of differentiation.

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.

Described herein are biomarkers comprising mTOR, PI3K / AKT, and MAPK / ERK signaling pathway members as well as cap-dependent translation initiation factors that enable monitoring and predicting responses to PD-1 pathway blockade in patients afflicted with cancers characterized by PD-1 expression.

The present invention discloses an Erk signal pathway inhibitor, and belongs to the field of cell biology. According to the present invention, the Mycobacterium tuberculosis secretory protein Mce3E capable of inhibiting the Erk1 / 2 signal pathway is firstly determined, and the Mce3E achieves the inhibition on the Erk1 / 2 signal pathway through spatial regulation on the Erk1 / 2 protein; the results of the present invention can provide new tools and ideas for the clinical treatment of various diseases, especially provide wide prospects in the fields of development, clinical application and the like of anti-tumor drugs and other drugs, and can further be directly used in the scientific research field or be used for guide the development of Erk1 / 2 inhibitor; and the result further provides the important theoretical significance for finding of the new drug target and screening of the new drug.

The invention provides an application of a DNA tetrahedron in the aspect of improving anti-aging process of cells. The DNA tetrahedron is synthesized from four DNA single chains in a self-assembling manner, wherein the sequences of the four single chains are represented as the SEQ ID No.1-4. The anti-aging process of cells includes anti-inflammation and anti-oxidizing processes, wherein the anti-inflammation effect, improved by the DNA tetrahedron, of the cells is achieved by reducing release of inflammatory cytokines and inhibiting expression quantities of iNOS gene and iNOS protein; the anti-oxidizing of the cells is achieved by inhibiting the phosphorylation of proteins ERK1 / 2, P38 and JNK at the downstream of MAPK / ERK signal channel, and improving the expression quantity of inducing heme oxygenase-1. The DNA tetrahedron has excellent bioavailability and biocompatibility, has anti-inflammation and anti-oxidizing functions and further delays senility of cells.

The invention relates to an MEK1 protein blocker and application thereof in preparing antiviral drugs. The MEK1 protein blocker provided by the invention can lower MEK1 protein level in cells through specificity or inhibit activation of MEK1 protein through specificity, so as to inhibit viral multiplication relying on host cell RAF / MEK / ERK signal channels. The invention specifically provides an MEK1 protein blocker which is a siRNA molecule combined with specificity of mek1 mRNA. The SODN nucleotide sequence thereof is shown as SEQ ID No: 1, and the ASODN nucleotide sequence thereof is shown as SEQ ID No: 2. The MEK1 protein blocker can inhibit viral multiplication relying on host cell RAF / MEK / ERK signal channels without affecting MEK2 protein level and functions, has single anti-virus target, security to organisms and wide antivirus spectrum, can overcome the problem of virus variation, and can be developed into a novel anti-virus drug.

Methods for differentiating human pluripotent stem cells to dorsal neuroectoderm progenitors and further to glial progenitor cells and oligodendrocyte progenitor cells (OPCs) using inhibitors of BMP signaling and MAPK / ERK signaling are provided. Also provided are cells and cellular compositions obtained by such methods, and uses of such cells. Further provided are methods and protocols for efficiently differentiating human pluripotent stem cells to OPCs in the absence of the ventralizing morphogen SHH or a SHH signaling activator. The methods of the present disclosure reproducibly produce dorsal neuroectoderm progenitor cells by day 7 of the differentiation process, glial progenitor cells by day 21 of the differentiation process and OPCs by day 42 of the differentiation process.

The invention provides an application of TMSB10 in diagnosis and treatment of glioma. Specifically, research finds that expression of TMSB10 increases with malignancy degree of glioma and is negativecorrelation with the survival rate. The TMSB10 silences and inhibits proliferation, attack and migration (MMP-9 and N-Cadherin) in U87MG and U251 cell lines, induces cell apoptosis, inhibits in-vitrocell cycles (p21, CDK4 and cyclin D1) through PI3K-AKT / ERK signal pathways (PI3K, P-AKT and p-ERK) and reduces in-vivo tumorigenicity. It indicates that the TMSB10 is an oncogene participating in occurrence and development of glioma and can be used as a biomarker and treatment target of the glioma.

The invention relates to a 5-pyrimidine-6-oxygen-pyrazolopyridine derivative and a pharmaceutically acceptable salt thereof, and a preparation method and application thereof. The chemical structural formula (II) of the 5-pyrimidine-6-oxygen-pyrazolopyridine derivative is shown in specification. The derivative and pharmaceutically acceptable salts thereof play anti-fibrotic effects by blocking theTGF-beta / ERK signaling pathway by activating a sGC-cGMP pathway. Therefore, as a novel sGC agonist, the 5-pyrimidine-6-oxygen-pyrazolopyridine derivative plays anti-fibrosis and anti-tissue remodeling effects by up-regulating cGMP levels, and becomes a new drug treatment strategy for pulmonary fibrosis diseases.

The present invention relates to a carbamate compound. The compound can block the formation of tumor new vessels by inhibiting a VEGF receptor and can also inhibit the Raf / MEK / ERK signal conduction path so as to achieve the effect of treatment of cancer. The present invention also relates to a preparation method of the compounds and application thereof in treatment or prevention of tumors, or in preparing a pharmaceutical composition for treating or preventing tumors.

The invention relates to the technical field of biology. High expression of kinase insert domain receptors (KDR) and platelet-derived growth factor receptors alpha (PDGFRA) can be viewed in multiple tumor tissues; and sorafenib directly inhibits tumor growth by inhibiting the activities of the KDR and the PDGFR and inhibiting a recombinant activated factor / methyl ethyl ketone / extracellular signal-regulated kinase (RAF / MEK / ERK) signal transduction pathway, and blocks the formation of new tumor vessels by inhibiting vascular endothelial growth factors (VEGF) and platelet-derived growth factors (PDGF), so that the sorafenib achieves double inhibiting and multi-target blocking anti-hepatic cell carcinoma (HCC) effects. Detection of KDR and PDGFR mRNA levels can assist doctors in forecasting the curative effect of medicaments and the clinical outcome of patients, and has important clinical significance. The invention aims to provide a kit capable of quickly, conveniently, sensitively and specifically detecting expression quantities of related genes KDR and PDGFRA of a sorafenib chemotherapeutic medicament. According to the kit, the KDR and PDGFR mRNA levels are detected by adopting a fluorescent quantitative polymerase chain reaction (PCR) technology with high sensitivity and specificity, so that the sensitivity and the specificity are remarkably improved; and the kit is quick in detection and high in flux, and can finish the detection in 3 to 4 hours.

The invention related to the use of high-density loss of heterozygosity (LOH) mapping in lung adenocarcinoma to identify intragenic LOH and driver mutations in different domains of ALK resulted in enhanced tumor growth in xenografted mouse. Mutant (H694R and E1384K) ALKs showed activation of Y1604 ALK and downstream AKT, STAT3 and ERK signaling pathways. Increases of oncogenic signalings resulted in enhanced cell proliferation, colony-formation, cell-migration and tumor-growth in xenografted mouse. Western blot and immunohistochemistry analysis using antibody against phospho-Y1604 ALK on 11 lung cancer cell-lines and 263 cancer specimens indicated ALK activation in all lung cancers regardless of tumor stages. Treating mutant-bearing mice with ALK inhibitor WHI-P 154 resulted in tumor shrinkage, metastasis suppression, and improved survival. Hyperphosphorylation of Y1604 ALK occurred early and continuously throughout tumor progression and could be used as a biomarker to detect lung cancer. Oncogenic ALK point mutations could be treatment targets for lung cancer.

The invention discloses an application of a D374Y mutant of PCSK9 protein in hepatoma cell migration restraining. The provided application is concretely any one of the following applications that a1: a product which restrains hepatoma cell migration is prepared and a2: the hepatoma cell migration is restrained of protein shown in a first sequence of a sequence table. An experiment proves that overexpression of the D374Y mutant of the PCSK9 protein has no obvious effect on the multiplication capacity of HepG2 cells but can obviously restrain the migration capacity of the cells; restraining of the D374Y mutant of the PCSK9 protein for hepatoma cells is acted through regulating and controlling of an ErK signal channel. The application has significant meaning on treatment of hepatomas.

The invention relates to the field of biotechnology, and particularly relates to application of an EGFR / ERK / TRIM32 signal path in promoting differentiation of spinal nerve stem cells after spinal cordinjury. According to the application, inhibitors or blockers of the EGFR / ERK / TRIM32 signal path and TRIM32 can be used for promoting the differentiation of the neural stem cells into neurons during the spinal cord injury repair process. After the spinal cord injury, a myelin protein finally inhibits a downstream target TRIM32 protein by activating the EGFR / ERK signal path, and further inhibitingthe differentiation of the neural stem cells into the neurons. The EGFR / ERK / TRIM32 signal path can be used as a new drug target for the spinal cord injury repair, and provides new ideas for repair andtreatment of the spinal cord injury repair.

The invention discloses an application of a D374Y mutant of PCSK9 protein in hepatoma cell migration restraining. The provided application is concretely any one of the following applications that a1: a product which restrains hepatoma cell migration is prepared and a2: the hepatoma cell migration is restrained of protein shown in a first sequence of a sequence table. An experiment proves that overexpression of the D374Y mutant of the PCSK9 protein has no obvious effect on the multiplication capacity of HepG2 cells but can obviously restrain the migration capacity of the cells; restraining of the D374Y mutant of the PCSK9 protein for hepatoma cells is acted through regulating and controlling of an ErK signal channel. The application has significant meaning on treatment of hepatomas.

The invention relates to the technical field of biology. High expression of kinase insert domain receptors (KDR) and platelet-derived growth factor receptors alpha (PDGFRA) can be viewed in multiple tumor tissues; and sorafenib directly inhibits tumor growth by inhibiting the activities of the KDR and the PDGFR and inhibiting a recombinant activated factor / methyl ethyl ketone / extracellular signal-regulated kinase (RAF / MEK / ERK) signal transduction pathway, and blocks the formation of new tumor vessels by inhibiting vascular endothelial growth factors (VEGF) and platelet-derived growth factors (PDGF), so that the sorafenib achieves double inhibiting and multi-target blocking anti-hepatic cell carcinoma (HCC) effects. Detection of KDR and PDGFR mRNA levels can assist doctors in forecasting the curative effect of medicaments and the clinical outcome of patients, and has important clinical significance. The invention aims to provide a kit capable of quickly, conveniently, sensitively and specifically detecting expression quantities of related genes KDR and PDGFRA of a sorafenib chemotherapeutic medicament. According to the kit, the KDR and PDGFR mRNA levels are detected by adopting a fluorescent quantitative polymerase chain reaction (PCR) technology with high sensitivity and specificity, so that the sensitivity and the specificity are remarkably improved; and the kit is quick in detection and high in flux, and can finish the detection in 3 to 4 hours.

The invention discloses application of 3-acetyl-11-keto-beta-boswellic acid to preparation of a drug for treating periprosthetical osteolysis, and relates to the technical field of drug application. The 3-acetyl-11-keto-beta-masticinic acid inhibits RANKL induced osteoclast activation by controlling an ERK signal passageway, so as to reduce the release of TNF-alpha, IL-1beta and IL-6 inflammatoryfactor; therefore, the periprosthetical osteolysis caused by wear particles is relieved.

The invention discloses the use of an L-Plastin gene, which is an application of the L-Plastin gene as a drug target in screening a type I hypersensitivity targeted therapeutic inhibitor, and the invention is induced by constructing a sensitizer C48 / 80 The P815 mast cell in vitro allergy model found that L-Plastin knockdown has the effect of inhibiting mast cell activation, can effectively inhibitthe degree of degranulation of mast cells in sensitized state, and relieve the release of histamine and beta-hexosaminidase Represses the synthesis and secretion of inflammatory factors; inhibits theexpression of inflammatory genes and the expression of key receptors in the mast cell activation pathway, and significantly inhibits the RAF-MEK-ERK signaling pathway and inhibits AKT in the intracellular signaling pathway. Phosphorylation levels have been shown to have anti-allergic effects at the cellular level, providing a theoretical basis for clinical treatment of type I hypersensitivity reactions and the application of screening for new drug targets.

The invention discloses application of theaflavin-3, 3'-digallate, and particularly relates to application of theaflavin-3, 3'-digallate in preparing a periprosthetical osteolysis drug. Compared with the prior art, theaflavin-3, 3'-digallate has the advantages that when the drug is adopted to treat periprosthetical osteolysis, bone surface lacuna number and lacuna area are obviously reduced, bone density and bone volume fraction are obviously increased, osteolysis degree is obviously lowered, periprosteal thickening degree is lowered, and mature osteoclast number is reduced; the drug can inhibit RANKL-induced osteoclast activation, and inhibition effect is dependent on concentration; the drug can obviously inhibit activation of an ERK signal path, can inhibit expression of ERK downstream target factors C0fos and NFATc1 and has no influence on activity of ERK upstream regulated kinase MEK1 / 2.

The present invention relates to a pharmaceutical composition for preventing and treating cancer or inflammatory disease, containing an NDRG3 expression or activity inhibitor as an active ingredient. Furthermore, the present invention relates to an NDRG3 protein-specific antibody and a use thereof. Specifically, the antibody to the NDRG3 protein is prepared, and the antibody is used to verify that NDRG3 mediated by lactate generated from a hypoxia reaction promotes cell proliferation, angiogenesis, and cytokine expression through the lactate-NDRG3-c-Raf-ERK signaling pathway, and thus the antibody binding to the epitope of the NDRG3 or a fragment of the antibody can be favorably used in the research of cancer or inflammation occurrence mechanism, the development of novel genes involved in the mechanism, and the development of therapeutic agents and new pharmaceuticals.

The invention consists in that substances acting as cascade inhibitors of the Raf / MEK / ERK signaling pathway, in particular MEK inhibitors, are used for the production of a drug for the preventive and antiviral therapy against DNA and RNA viruses, in particular against intranuclear-replicating negative strand RNA viruses, for instance influenza or Borna disease viruses.

The invention discloses an application of small molecule inhibitors VX-11e and BVD-523 in inhibiting chlamydia infection. The research found that the signal pathway inhibitors VX-11e and BVD-523 can obviously inhibit the infection of the chlamydia trachomatis, and have significant difference compared with the reported MEK inhibitor U0126; according to the application of small molecule inhibitors VX-11e and BVD-523 in inhibiting chlamydia infection, the small molecule inhibitors VX-11e and BVD-523 are applied to chlamydia infection for the first time, and are expected to be new drugs for chlamydia targeting host therapy; the research also found that inhibitors VX-11e and BVD-523 had synergistic effect with azithromycin. After chlamydia infection, VX-11e and BVD-523 could promote the anti-infection effect of azithromycin, which was of great value in the treatment of chlamydia infection. The application of small molecule inhibitors VX-11e and BVD-523 in inhibiting chlamydia infection hasimportant significance for the development of new drugs for chlamydia trachomatis infection and the search of new targets for auxiliary host therapy.