110 results about "Mitogen-activated protein" patented technology

This invention relates to compounds, compositions, and methods useful for modulating mitogen activated protein kinase (MAP kinase) gene expression using short interfering nucleic acid (siNA) molecules. This invention also relates to compounds, compositions, and methods useful for modulating the expression and activity of other genes involved in pathways of MAP kinase gene expression and / or activity by RNA interference (RNAi) using small nucleic acid molecules. In particular, the instant invention features small nucleic acid molecules, such as short interfering nucleic acid (siNA), short interfering RNA (siRNA), double-stranded RNA (dsRNA), micro-RNA (miRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of MAP kinase genes, such as Jun amino-terminal kinase (e.g., JNK-1, JNK-2), p38 (MAPK 14), ERK (e.g., ERK-1, ERK-2) and / or c-Jun.

This invention relates to a method for prevention and treatment of aging, age-related disorders and / or age-related manifestations including atherosclerosis, peripheral vascular disease, coronary artery disease, osteoporosis, type 2 diabetes, dementia and some forms of arthritis and cancer in a subject comprising administering to said subject, separately, sequentially or simultaneously a therapeutically effective dosage of each component or combination of statins, bisphosphonates, cholesterol lowering agents or techniques, interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, serine / threonine kinases inhibitors / antibodies, mitogen-activated protein (MAP) kinase inhibitors / antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors / antibodies, Nuclear factor κB (NF-κB) inhibitors / antibodies, IκB kinase (IKK) inhibitors / antibodies, activator protein-1 (AP-1) inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof, administered separately, in sequence or simultaneously. Inhibition of the signal transduction pathway for Interleukin 6 mediated inflammation is key to the prevention and treatment of atherosclerosis, peripheral vascular disease, coronary artery disease, aging, age-related disorders and / or age-related manifestations including osteoporosis, type 2 diabetes, dementia and some forms of arthritis and tumors. Inhibition of Interleukin 6 mediated inflammation may be achieved indirectly through regulation of endogenous cholesterol synthesis and isoprenoid depletion or by direct inhibition of the signal transduction pathway utilizing interleukin-6 inhibitor / antibody, interleukin-6 receptor inhibitor / antibody, interleukin-6 antisense oligonucleotide (ASON), gp130 protein inhibitor / antibody, tyrosine kinases inhibitors / antibodies, serine / threonine kinases inhibitors / antibodies, mitogen-activated protein (MAP) kinase inhibitors / antibodies, phosphatidylinositol 3-kinase (PI3K) inhibitors / antibodies, Nuclear factor κB (NF-κB) inhibitors / antibodies, IκB kinase (IKK) inhibitors / antibodies, activator protein-1 (AP-1) inhibitors / antibodies, STAT transcription factors inhibitors / antibodies, altered IL-6, partial peptides of IL-6 or IL-6 receptor, or SOCS (suppressors of cytokine signaling) protein, or a functional fragment thereof. Said method for prevention and treatment of said disorders is based on inhibition of Interleukin-6 inflammation through regulation of cholesterol metabolism, isoprenoid depletion and / or inhibition of the signal transduction pathway

There are provided compounds of formula I,wherein:Y represents NR2R3;one of R2 and R3 represents —[C2-4 alkylene-O]1-12—[C2-4 alkylene]-R2a and the other of R2 and R3 has a meaning given in the description; andR, R1, R2a, Ra, Rb, Q, X and Y have meanings given in the description,which compounds have antiinflammatory activity (e.g., through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

A method of diagnosing Alzheimer's disease in a patient comprises determining whether the phosphorylation level of an indicator protein in cells of the patient after stimulus with an activator compound is abnormally elevated as compared to a basal phosphorylation level, the indicator protein being e.g. Erk1 / 2 and the activator compound being e.g. bradykinin.

The present invention relates to compositions and methods useful in treating diseases and disorders related to protein kinases. In particular, the present invention relates to compositions and methods useful for targeting protein kinases related to mitogen activated protein kinase (MAPK) pathways (e.g., p38 MAPK, JNK, ERK, and upstream and downstream protein kinases) and / or casein kinase (CK) pathways (e.g., CK1δ, and upstream and downstream protein kinases), and diseases and disorders related to MAPK pathways (e.g., p38 MAPK, JNK, ERK, and upstream and downstream protein kinases) and / or CK pathways (e.g., CK1δ, and upstream and downstream protein kinases).

The present invention is used for evaluating the advantages of haliotis discus hannai. A multi-phase HPLC purification system is used to purify anti-inflammatory peptide from abalone (AAIP, abalone anti-inflammatory peptide). In tandem MS analysis, a fragmentation result shows that the amino acid sequence of the AAIP with nitrogen monoxide (NO) inhibitory activity (IC50=55.8[um]M) is Pro-Phe-Asn-Glu-Gly-Thr-Phe-Ala-Ser (1175.2Da). While the anti-inflammatory effect of RAW264.7 macrophages generated by the stimulus of the AAIP to lipopolysaccharides (LPS) is further studied, and the molecular mechanism is elaborated. The result shows that the AAIP peptide inhibits the nitrogen monoxide (NO) generation induced by the LPS through the expression of inducible nitric oxide synthase (iNOS) by a dose-dependent manner, and the gene transcription of pro-inflammatory cytokines is also obviously reduced, wherein the pro-inflammatory cytokines comprise such as interleukin (IL-1 beta), tumor necrosis factors (TNF-beta) and IL-6. In addition, the AAIP obviously inhibits phosphorylation of mitogen-activated protein kinases (MAPK), such as p-p38 and p-JNK. These results indicate that the AAIP inhibits inflammatory response induced by LPS by intercepting the MAPK pathway of the macrophages. Therefore, the AAIP can be applied to therapeutic drugs for inflammations treatment or healthcare food products.

There are provided compounds of formula I.wherein R1 to R5, X1, X2, Ar, L, A, A1, E and G have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

There are provided compounds of formula I,wherein R1 to R5, X1, X2, Ar, L, E, A, A1, G and G1 have meanings given in the description, which compounds have antiinflammatory activity (e.g. through inhibition of one or more of members of: the family of p38 mitogen-activated protein kinase enzymes; Syk kinase; and members of the Src family of tyrosine kinases) and have use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, eye and intestines.

Provided is a composition for reprogramming somatic cells to generate embryonic stem cell-like cells, comprising: a) a Bmi1 (B cell-specific Moloney murine leukemia virus integration site 1) protein or a nucleic acid molecule encoding the Bmi1 protein; and b) at least one low molecular weight substance selected from the group consisting of a set of a MEK / ERK (mitogen-activated protein kinase / extracellular regulated kinase) inhibitor and a GSK (glycogen synthase kinase) inhibitor, a set of a G9a HMTase (G9a histone methyltransferase) inhibitor and a DMNT (DNA methyltransferase) inhibitor, and a histone deacetylase inhibitor. Also, a method is provided for reprogramming somatic cells to generate embryonic stem cell-like cells using the composition. In addition to reducing the number of the reprogramming factors conventionally needed, the composition and method allow the generation of pluripotent embryonic stem cell-like cells which have high potential in the cell therapy of various diseases.

The invention is based upon the discovery that the mitogen-activated protein kinase (MAPK) pathway can increase CA9 expression independently of HIF-1, as well as increasing CA9 expression under HIF-1-dependent pathways initiated by hypoxia or high cell density. Disclosed herein are novel therapeutic methods for treating preneoplastic / neoplastic diseases associated with abnormal MN / CA IX expression, using MAPK pathway inhibitors. Preferably, the MAPK pathway inhibitors are raf kinase inhibitors, particularly the raf kinase inhibitor Sorafenib. Further disclosed are methods for patient therapy selection for MAPK pathway inhibitors, preferably in combination with other cancer therapies, based on detection of abnormal MN / CA9 gene expression in preneoplastic / neoplastic tissues.

Methods for enhancing the suppressive function of myeloid derived suppressor cells (MDSCs) for the treatment of autoimmune diseases using small compounds are disclosed. In certain aspects, the small compounds are glatiramer acetate and mitogen activated protein (MAP) kinase inhibitors. In other aspects, these methods include the administration of exogenous MD-SCs or the use of endogenous MDSCs mobilized using stem cell mobilizers. In yet other aspects, compositions containing MDSCs and small compounds of the invention are provided.

The present invention relates to the mitogen-activated protein kinase called MAPK5. The rice MAPK5 gene, its protein and kinase activity were induced by abscisic acid, pathogen infection, wounding, drought, salt and cold temperature. However, suppression of MAPK5 expression and kinase activity in dsRNAi transgenic plants resulted in constitutive expression of pathogenesis-related genes such as PR-1 and PR-10 but enhanced resistance to fungal and bacterial pathogens. In contrast, overexpressed transgenic lines exhibited elevated MAPK5 kinase activity and increased tolerance to drought, salt and cold stresses. This invention provides methods for increasing tolerance to abiotic and biotic stress in plant using MAPK5.

The invention relates to a cloned protein kinase gene of rice related to salt endurance and the application. The protein kinase gene codes a mitogen activating protein kinase (MAP3K), which is the following protein (i) or (ii): the amino acid sequence with SEQ ID NO: 1 in the sequence table; (ii) the protein derived from (i) with the function of controlling salt endurance of plants after replacing, missing or adding a to ten amino acid residues in the amino acid sequences limited by (i). The cloned protein kinase gene of rice related to salt endurance has the advantages that: the experiment proves that using the gene to transform the rice can significantly increase the salt endurance of rice without evidently influencing the normal growth and economic characters of the rice; the protein and the coding gene have important theoretical and practical significance to the improvement of salt endurance and related characters of the plant as well as the study on tolerance mechanism of the plant in adverse circumstances.

The present invention relates to a composition and a method for generating induced pluripotent stem cells using the same Provided is a composition for reprogramming somatic cells to generate embryonic stem cell-like cells, comprising: a) a Bmi1 (B cell-specific Moloney murine leukemia virus integration site 1) protein or a nucleic acid molecule encoding the Bmi1 protein; and b) at least one low molecular weight substance selected from the group consisting of a set of a MEK / ERK (mitogen-activated protein kinase / extracellular regulated kinase) inhibitor and a GSK (glycogen synthase kinase) inhibitor, a set of a G9a HMTase (G9a histone methyltransferase) inhibitor and a DMNT (DNA methyltransferase) inhibitor, and a histone deacetylase inhibitor. Also, a method is provided for reprogramming somatic cells to generate embryonic stem cell-like cells using the composition.

The present invention discloses a kind of rice mitogen-activated protein kinase and its coding gene and application in breeding very high yield rice variety. The kinase protein with one of the following amino acid residue sequence: 1) SEQ ID No. 1 in the sequence list; and 2. the amino acid residue sequence of SEQ ID No. 1 through substitution, deletion or addition of 1-10 amino acid residues and coding rice grain growth related protein. By means of transgenic technology, the present invention improves the effect of OsMAPK6 on grain shape construction to regulate the activity of grain in accumulating matter and reach the aim of increasing rice yield.

The present disclosure relates to compounds of formula (I):which are inhibitors of p38 mitogen-activated protein kinase enzymes, particularly the alpha and gamma kinase sub-types thereof, and their use in therapy, including in pharmaceutical combinations, especially in the treatment of inflammatory diseases, including inflammatory diseases of the lung, such as COPD

The invention discloses an application of cycloicaritin in preparation of an anti-tumor composition. The cycloicaritin disclosed by the invention can effectively inhibit growth and pipe formation of HUVEC (Human Umbilical Vein Endothelial Cells) and cause apoptosis to inhibit migration of the HUVEC, and has a remarkable inhibiting effect on highly activated MAPK (Mitogen-Activated Protein Kinase) pathway and AKT pathway. Through the above mechanism, the composition can effective prevent tumors, and particularly can effectively inhibit growth of liver cancer, breast cancer, lung cancer, cervical cancer and colon cancer.

The invention provides novel means to inhibit the Mitogen Activated Protein Kinases (MAPKs) pathway activated by Ras / Raf complex using GILZ protein related compounds as inhibitors of Raf / Ras-mediated signal transduction. Pharmaceutical compositions containing such compounds are also disclosed.

The invention relates to phenanthrene and dihydrophenanthrene compounds and an application thereof. The phenanthrene or dihydrophenanthrene compounds can effectively inhibit inflammatory factors and also can inhibit NF (nuclear factor)-kappa B and MAPKs (Mitogen Activated Protein Kinase) signal channels. The compounds or medically acceptable salts, solvates, clathrate compounds or prodrugs thereof can be applied to serving as medicines for treating inflammations and also can be applied to serving as medicines for treating NF-kappa B and MAPKs signal channel related diseases.

The invention belongs to the field of plant genetic engineering, and particularly relates to a poncirustrifoliata mitogen-activated protein kinase (PtrMAPK) gene which is obtained from poncirustrifoliata by separation and cloning. The nucleotide sequence of the gene is shown as a sequence table SEQ ID NO:1; the corresponding amino acid sequence of the gene is shown as a sequence table SEQ ID NO:2; and the gene comprises 1128bp of open reading frame, and encodes 375 amino acids, an isoelectric point is 5.51, and predicted molecular weight is 43kD. The PtrMAPK gene is imported into tobacco for functional verification, and the drought resistance capacity of the obtained transgenic tobacco plant can be improved obviously. New gene resources are provided for anti-abiotic stress molecular design and breeding, new genetic resources are provided for implementing green and environment-friendly agriculture, and the development and utilization of the genetic resources contribute to reducing agriculture production cost and achieving environment-friendliness.

The present invention relates to compositions and methods useful in treating diseases and disorders related to protein kinases. In particular, the present invention relates to compositions and methods useful for targeting protein kinases related to mitogen activated protein kinase (MAPK) pathways (e.g., p38 MAPK, JNK, ERK, and upstream and downstream protein kinases) and / or casein kinase (CK) pathways (e.g., CK1δ, and upstream and downstream protein kinases), and diseases and disorders related to MAPK pathways (e.g., p38 MAPK, JNK, ERK, and upstream and downstream protein kinases) and / or CK pathways (e.g., CK1δ, and upstream and downstream protein kinases).

The invention relates to crystalline molecules or molecular complexes that comprise binding pockets of mitogen activated protein kinase activated protein kinase 2 (MAPKAPK2) or its homologues. The invention also relates to crystals comprising MAPKAPK2. The present invention also relates to a computer comprising a data storage medium encoded with the structural coordinates of MAPKAPK2 binding pockets and methods of using a computer to evaluate the ability of a compound to bind to the molecule or molecular complex. This invention also relates to methods of using the structure coordinates to solve the structure of homologous proteins or protein complexes. In addition, this invention relates to methods of using the structure coordinates to screen for, design and optimize compounds, including agonists and antagonists, which bind to MAPKAPK2 or homologues thereof.

The invention relates to a gossypium hirsutum mitogen-activated protein kinas 6 (GhMAPK6) gene and application thereof, belonging to the fields of molecular biology and biotechnology. The GhMAPK6 gene is obtained by adopting homologous cloning and RACE [Rapid-Amplification of cDNA (complementary Deoxyribonucleic Acid) Ends] technology. The cDNA sequence of the gene is put under a CaMV 35S promoter to construct a plant expression vector, and nicotiana benthamiana is transformed to excessively express the gene in tobacco. An experiment proves that a transgenic tobacco plant has remarkably improved yield than a non-transgenic tobacco plant in the aspects of increase in the leaf area, increase in the tillering number, increase in the infruit number and increase in the ripening rate. Therefore, the gene has important realistic significance in improving the crop yield trait and increasing the crop yield by a gene engineering way according to the yield increasing property of the gene.

The invention belongs to the technical field of medicines, in particular relates to a physalin A extracting process and medical application thereof, in particular relates to a novel application of physalin A in preparation of an anti-tumor dug and in particular relates to the use of physalin A in treatment of human fibrosarcoma and human malignant melanoma. After process optimization, the extracting rate of physalin A is 0.2133%. Physalin A can be used for inhibiting the growth of various tumor cells, particularly has obvious inhibiting action on the growth of the human fibrosarcoma and human malignant melanoma, but does not inhibit the activities of the human normal cells obviously. The mechanism is that the downstream caspase family-associated protein is activated by activating Fas death receptors, so that the tumor cells are induced to generate apoptosis. Meanwhile, the physalin A can be used for inducing the tumor cells to generate autophagy for achieving autophagy antagonism apoptosis in the HT1080 and the A375-S2 cells; and the p53 protein and the MAPK (Mitogen-Activated Protein Kinase)-familty p38 protein have a key regulation effect. The physalin A can be used for preparing a digestive tract dosage form or a non-digestive tract dosage form, which can be used for treating tumors including the human fibrosarcoma and human malignant melanoma.

The present invention relates to altering the levels of Th2 cytokine production, and in particular, biasing the cytokine expression profile towards Th2 cytokine production through mitogen-activated protein kinase / ERK kinase kinase 1 (MEKK1), the screening of agents that increase Th2 cytokine production, and the treatment of Th1 associated autoimmune diseases in vivo. In one embodiment, the present invention relates to agents including but not limited to reducing the activity of MEKK1, leading to increased levels of Th2 cytokine production.

The invention relates to a rape mitogen-activated protein kinase gene (Mitogen Activated Protein Kinase, MAPK), in particular to a ubiquitous protein in ubiquitous (rape), the ubiquitous protein is an important element in an eucaryon signal transmission network; the protein is closely related to the plant diseases and insect pests resistance of the rape, the nucleotide sequence and amino acid sequence thereof are shown in a sequence table SEQ ID NO:1 and SEQ ID NO:2. The rape mitogen-activated protein kinase gene has the advantages that: the rape mitogen-activated protein kinase gene has obvious guiding function to the application of biopesticide; the gene clone is valuable to a molecule signal channel which discloses chitosan oligosaccharide induction plant defense responses and has important theoretical direction significance to the application of the oligosaccharide biopesticide.

The invention belongs to the technical field of medicine, discloses an application of a MAPK (mitogen-activated protein kinase) signaling pathway inhibitor in preparation of a PD (Parkinson's disease) treatment drug and particularly provides an application of the MAPK signal pathway inhibitor in preparation of a drug for delaying dopaminergic neuron degeneration. A product can effectively delay degenerative death of dopaminergic neurons, and the PD is treated fundamentally; the treatment effect of the drug can be realized through oral administration instead of injection, and the drug has a better curative effect on PD caused by various reasons and has great significance on treatment and healing of PD.