68results about How to "Reduce phosphorylation" patented technology

Disclosed are compositions and methods for modulating hemichannel function in a cell, tissue or organ. The invention also relates to useful screens for detecting such compounds, particularly those capable of modulating connexin phosphorylation. Further provided are therapeutic methods for preventing or treating conditions impacted by undesired hemichannel function in a mammal such as heart arrhythmia.

The invention discloses pyridylpyrimidyl amine compounds or pyridylpyridyl amine compounds disclosed as Formula I and application thereof in preparing antineoplastic drugs, belonging to the technical field of drugs. The compounds can selectively inhibit CDK4 and CDK6, enable G1-period tumor cells to stop growth and G1-period tumor cells to reduce, can effectively lower the phosphorylation of the tumor inhibiting protein Rb in the Ser780 site, and thus, can be used for various diseases caused by cell cycle control maladjustment participated by CDK4 and CDK6. The compounds are especially suitable for treating malignant tumors, and have the characteristics of high selectivity, high activity and high tumor cell proliferation resistance.

The present invention includes the disclosure of the hPER2 gene and a mutant of the hPER2 gene that participates in the human circadian biological clock. The product of the mutant hPER2 gene found in some familial advanced sleep phase syndrome patients is hypophosphorylated by casein kinase epsilon due to the serine-to-glycine mutation caused by the point mutation of the genomic sequence. Specifically, this serine-to-glycine mutation affects the casein kinase epsilon binding region of the hPER2 protein, thus blocking the phosphorylation cascade ordinarily caused by the binding of casein kinase epsilon to hPER2.

This invention provides compounds having the structure

which may be used for the treatment of tumors.

Provided herein are compositions and methods for inhibiting cancer cell motility and/or metastasis. In particular embodiments, KBU2046 (or an analog thereof) and one or more additional therapies (e.g., cancer therapies (e.g., hormone therapies and chemotherapies) are provided to inhibit cancer cell motility, inhibit metastasis, and/or treat cancer (e.g., prostate cancer, lung cancer, breast cancer, colon cancer, etc.).

The present invention provides a cell culture enriched for sphingolipid enhances neural stem cells (SENSe), particularly oligodendrocyte precursor cells (ODPCs), that do not form teratomas after transplanted in vivo. Methods for producing and use of the invention ODPCs or the cell culture enriched with these ODPCs for stem cell therapy are also provided. The invention method comprises culturing a stem cell culture with a cell culture medium comprising a ceramide compound and a S1P receptor agonist in sequence, overlapping intervals or concurrent manners. The present invention further provides a cellular or gene therapy using a composition comprising a ceramide compound in conjunction with a S1P₁ agonist to proliferate or differentiate endogeneous neural stem cells to ODPCs and further to oligodendrocytes.

This invention provides methods for detecting serum GEP level. This invention further provides methods for determining whether a subject is afflicted with Hepatocellular carcinoma (HCC) by measuring serum GEP level. In another embodiment, this invention provides methods for the suppression of HCC growth and progression both in vitro and in vivo by treating a patient with anti-GEP monoclonal antibody A23.

The invention discloses a beta-carboline GSK3beta/DYRK1A dual inhibitor as shown in a general formula I, a preparation method of the beta-carboline GSK3beta/DYRK1A dual inhibitor and application of the beta-carboline GSK3beta/DYRK1A dual inhibitor in resistant the Alzheimer's disease. A novel beta-carboline derivative has GSK3beta/DYRK1A dual inhibition activity, and a preparation method of the beta-carboline derivative serving as the GSK3beta/DYRK1A dual inhibitor is provided. Meanwhile, the invention also discloses application of the beta-carboline derivative in preparation of a medicine for treating the Alzheimer's disease. The beta-carboline derivative can provide a theoretical basis for discovery of a novel AD treatment drug.

The invention discloses a pulmonary hypertension virulence gene ACVRL1 mutation site and an application thereof. The amino acid sequence of a protein provided by the invention is sequence 4. The DNA molecule of the protein is coded and the nucleotide sequence of the DNA molecule is sequence 2. The experiment shows that the novel ACVRL1 gene mutation site is related to the pulmonary hypertension, by means of detecting whether the novel gene mutation site is the mutation site, whether the sample to be tested suffers from pulmonary hypertension can be predicted; and the novel gene mutation site can be used as a target for treating the pulmonary hypertension, and a new therapy pathway for researching the pulmonary hypertension drugs can be provided. The cell experiment verifies that the ACVRL1 gene mutation site is capable of reducing the SMAD1 and SMAD5 protein phosphorylation and/or increasing the BMP transcriptional activity in the cell.

The invention discloses a GSK-3beta/ChE double inhibitor with the structural formula shown as formula (I), or pharmaceutically acceptable salts and solvates of formula (I). The chemical small molecules involved in the invention can effectively inhibit the enzyme activity of GSK-3 beta, AChE and BChE, have the effects of improving cognition, reducing tau protein phosphorylation and reducing neuroinflammation, and have important application value in the preparation of drugs for preventing or treating Alzheimer's disease.

Polyclonal antibody specific for a phosphorylated linker region in Smad2 and/or Smad3.

The present invention relates to the use of selenate or a pharmaceutically acceptable salt thereof in methods and compositions for enhancing the activity of the protein phosphatase PP2A. Methods of reducing phosphorylation of tau protein, inhibiting activity of GSK3 and treating or preventing neurodegenerative diseases are also described.

The invention discloses a research method for the pharmacologic action of mangiferin on mouse diabetes. The research method comprises material selection and an experimental method, biochemical parameter evaluation, histological analysis, measurement of reactive oxygen species (ROS), determination of malondialdehyde (MDA) and antioxidase, analysis of renal tissue inflammatory factors, immunofluorescent staining, Western blotting and statistic analysis. According to the research method, a trichrome staining method is utilized to observe renal morphology; a kit is utilized to determine a blood biochemical index; levels of inflammatory cytokines, the antioxidase, the MDA and the ROS are determined; expression of fibronectin, collagen I and alpha-SMA is detected by an immunohistochemical method, and regulation of paths of TGF-beta 1 and phosphatase and tensin homolog/phosphatidylinositol 3-hydroxy kinase/protein kinase B (PTEN/PI3K/Akt) is detected by Western blotting; researches show thatthe mangiferin can significantly improve the renal dysfunction of diabetic mice; renal interstitial fibrosis can be prevented by reducing positive expression of fibronectin (FN), collagen type I (ColI) and alpha-smooth muscle actin (SMA) during therapy with the mangiferin; and meanwhile, mangiferin increases the antioxidase, reduces phosphorylation of the PI3K and Akt, inhibits the renal interstitial fibrosis, and provides more theoretical foundations for clinical application of traditional Chinese medicine in treating diabetes.

The present invention relates to methods of treating or preventing a metabolic disorder in a subject, methods of treating or preventing coronary artery disease in a subject with a metabolic disorder, as well as methods of reducing hepatic glucose production in a subject. Such methods include, but are not limited to, the administration to the subject of inhibitors or activators of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1, Dach2, or any combination thereof. The invention also provides methods of identifying a compound that inhibits the activity of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2, or reduces the activity and/or activation of CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach, or activates CaMKII, IP3Rs, calcineurin, p38, MK2/3, HDAC4, Dach1 or Dach2.

The present invention provides methods of inhibiting a tau protein such as h-tau₄₂ or a biologically active fragment, derivative or analog thereof, methods of treating a disease caused by a tau protein such as h-tau₄₂, and methods to identify agents that may inhibit a tau protein such as h-tau₄₂. The methods for identifying an agent effective to inhibit a tau protein may feature administering an agent; and observing either i) a reduction in biological activity of the tau protein or a biologically active fragment, derivative or analog thereof or ii) a reduction in phosphorylation of the tau protein or a biologically active fragment, derivative or analog thereof.

The present invention provides methods and compositions for treatment of diseases and disorders. More specifically, the invention for the first time shows a link between IRAK-1 and phosphorylation of proteins involved in cardiovascular disease, diabetes, neurodegeneration, and associated diseases and disorders and complications. Typically, the diseases and disorders involve an inflammatory component. Assays for bioactive substances affecting IRAK-1 regulated progression of inflammation and diseases and disorders involving inflammation are also disclosed.