147 results about "Phosphatidylinositol" patented technology

This invention relates to a method for prevention and treatment of aging and age-related disorders 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 and age-related disorders 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.

The first aspect of the invention relates to a bispecific antibody, which comprises a first functional domain for specific identification of phosphatidylinositol protein polysaccharide-3, a second domain for specific identification of human T cell antigen CD3, and a connection for connecting the functional domains. The second aspect of the invention relates to a nucleotide sequence encoding the above antibody. The third aspect of the invention relates to a carrier containing the above nucleotide sequence, and includes an expressive vector. The fourth aspect of the invention relates to a eukaryotic or prokaryotic expression system containing the above carrier. The fifth aspect of the invention relates to application of the above antibody to preparation of medicament for treating or preventing tumor.

Particles having a tap density less than about 0.4 g / cm3 are formed by spray drying from a colloidal solution including a carboxylic acid or salt thereof, a phospholipid, a divalent salt and a solvent such as an aqueous-organic solvent. The colloidal solution can also include a therapeutic, prophylactic or diagnostic agent. Preferred carboxylic acids include at least two carboxyl groups. Preferred phospholipids include phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, phophstidylserines, phosphatidylinositols and combinations thereof. The particles are suitable for pulmonary delivery.

Medicinal compositions which are useful as phosphatidylinositol 3-kinase (PI3K) inhibitors and anticancer agents; and novel bicyclic or tricyclic condensed heteroaryl derivatives or salts thereof having favorable effects of inhibiting PI3K and suppressing the proliferation of cancer cells.

Attenuated influenza virus variants comprising substitutions in NS1 that interfere with viral replication and phosphatidylinositol 3-kinase activation are described. NS1 variant polypeptides, polynucleotides encoding NS1 variant polypeptides, a reverse genetics system for producing attenuated influenza virus NS1 variants, immunogenic compositions comprising live attenuated influenza virus NS1 variants, methods of stimulating an immune response against influenza virus, methods of interfering with influenza virus replication, and methods of treating and preventing influenza virus infection are described.

This invention relates to novel 2,3-dihydroimidazo[1,2-c]quinazoline compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for phosphotidylinositol-3-kinase (PI3K) inhibition and treating diseases associated with phosphotidylinositol-3-kinase (PI3K) activity, in particular treating hyper-proliferative and / or angiogenesis disorders, as a sole agent or in combination with other active ingredients.

The invention relates to the medical field of immunoassay, more specially, the invention provides a chemiluminescent immunoassay detection kit for phosphatidylinositol proteoglycan-3(GPC-3) and a preparation method thereof, and realizes the simultaneous serological detection of GPC-3 N terminal and C-terminal protein with the chemiluminescent immunoassay method. The kit has the advantages of simple sampling, convenient detection and accurate and specific technical method. The invention adopts a biotin-strapavidin system to coat antibodies and improve the efficiency of antibody coating and the linear range of detection as well as sensitivity, and can be conveniently used for the tracing observation of early diagnosis or treatment effect for primary carcinoma of liver.

A modified phospholipase D having an ability to synthesize phosphatidylinositol which contains: (A) an amino acid sequence derived from the amino acid sequence represented by SEQ ID NO:2 by substitution of at least one of the amino acid residues at the 187-, 191- and 385-positions by other amino acid residue(s); or (B) an amino acid sequence of a polypeptide derived from the amino acid sequence as described in the above (A) by substitution, deletion, insertion and / or addition of at least one amino acid residue at a position different from the 187-, 191- and 385-positions and having an ability to synthesize phosphatidylinositol. By using this modified phospholipase D, phosphatidylinositol can be efficiently produced from a phospholipid. It is also intended to provide a method of screening a phospholipase D having an ability to synthesize an acylglycerophospholipid having glycol group.

The invention belongs to the field of medical technology, and in particular relates to a selective phosphatidylinositol-3 kinase delta inhibitor shown in the formula (I), a salt of the selective phosphatidylinositol-3 kinase delta inhibitor, accepted in pharmacy, and a stereoisomer or a deuterated material of the selective phosphatidylinositol-3 kinase delta inhibitor, wherein X1, X2, X3, X4, Y, Z, W, R1 and R2 are defined as specification. The invention also relates to a preparation method of the compounds, medicinal preparations containing the compounds and application of the compounds in preparation of drugs for treating and / or preventing inflammatory diseases or tumors.

The invention discloses new application of a 2-(4-fluorophenyl)-3-nitro-8-O-ethyl-2-hydro-benzopyran compound, in particular application of the compound serving as phosphatidylinositol-3-kinase (PI3K) inhibitor. The PI3K inhibitor can inhibit PI3K and disturb a PI3K / AKT signal channel, has good treatment effect on multiple tumors, particularly malignant hematological diseases, can effectively control the propagation of tumor cells and induce the apoptosis thereof, and has the effect of inhibiting and treating the tumors; and meanwhile, the PI3K has low toxicity.

A liver cancer marker phosphatidylinositol proteoglycan 3 (Glypican-3, GPC3) is used as a research object, a GPC3 aptamer is used as a recognition probe, on the basis of good electron transfer effectand excellent loading capacity of a reductive graphene oxide-chitosan-ferrocene / nano platinum and palladium (Pt-Pd NPs / RGO-CS-Fc) composite material, the GPC3 aptamer can specifically recognize and becombined with GPC3 protein, and a novel aptamer sensor capable of performing specific recognition and quantitative analysis on the GPC3 protein is constructed and used for detecting the content of GPC3 in serum. The method is simple to operate, time-saving, low in cost and relatively low in detection limit.

The invention relates to a phosphatidylinositol proteoglycan GPC3 protein fragment, which has an amino acid sequence represented as the SEQ ID NO.1. The GPC3 protein fragment is strong in antibody specificity, can be used for preparing a polyclonal or monoclonal antibody being high in titer or preparing a GPC3 protein standard sample, and can be used in GPC3 protein detection, comprising detections of the content, the activity and the structure. The invention also relates to a monoclonal antibody hybridoma cell strain GPC3-1H5. A GPC3 antibody secreted from the GPC3-1H5 is high in yield and titer and is sensitive in reaction, so that the GPC3 antibody can improve sensitivity and accuracy of detection. The GPC3-1H5 can be widely applied in the detection of expression of the GPC3, can reduce the production cost of the GPC3 and is beneficial to clinical popularization and application of GPC3 detection.

This invention relates to novel sulfone 2I3-dihydroimidazo[1 l2-c]quinazoline compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for phosphotidylinositol-3-kinase (PI3K) inhibition and treating diseases associated with phosphotidylinositol-3-kinase (PI3K) activity, in particular treating hyper-proliferative and / or angiogenesis mediated disorders, as a sole agent or in combination with other active ingredients.

The present invention refers to the renin / prorenin receptor (RER) signal transduction pathway and, in particular, to the role of promyelocytic zinc finger protein (PLZF) and its downstream targets involved in this pathway, e.g. the p85α subunit of phosphatidylinositol-3 kinase (PI3K-p85α). In more detail, the present invention refers to a method for determination of RER activity, e.g. stimulation or inhibition of RER activity, using PLZF activity as a measurement from which RER activity is derived. For the determination of RER activity, use can be made of RER / PLZF protein interaction, PLZF translocation and / or PLZF recruitment. The present invention further refers to a use of said method for identifying RER ligands, e.g. pharmaceutically active agonists or antagonists, as well as for studying undesired side-effects of renin inhibitors.

The invention discloses a metabolite marker for diagnosing and distinguishing coronary atherosclerosis and stable angina pectoris. The metabolite marker includes one or more of phosphorylcholine, palmitoylethanolamine, phytosphingosine, phosphatidylcholine, ethyl chenodeoxycholic acid, lysophosphatidyl choline (16:0), lysophosphatidyl choline (18:2) and phosphatidyl inositol (20:4 / 0:0). When the single metabolite marker is used for diagnosing and distinguishing a patient suffering from the stable angina pectoris and a patient suffering from the coronary atherosclerosis, the ROC areas under the curve (AUC) are greater than 0.7, and the marker has clinical diagnostic significance. When the markers are combined for diagnosis, the AUC is further improved with the increase of the combination number; when all eight markers are combined, the AUC is the highest and is up to 0.985, and the sensitivity and specificity are 97.4% and 98.0% respectively under the condition of an optimal cutoff value. The metabolite marker can accurately diagnose and distinguish the coronary atherosclerosis and the stable angina pectoris and is high in accuracy and good in sensitivity and specificity.

The invention provides methods and compositions relating to molecular targets identified as being capable of increasing or decreasing thermogenic potential in cells, including preadipocytes. Included in the invention are methods and compositions relating to inhibiting or suppressing the activity of an uncoupling protein 1 (UCP1) negative regulator, such as cardiac actin 1 (ACTC1), somatostatin receptor 1 (SSTR1), FAT atypical cadherin 1 (FAT1), and protein tyrosine phosphatase receptor type B (PT-PRB). Also included in the invention are methods and compositions relating to activating a UCP1 positive regulator, such as phosphatidylinositol-3,4,5-triphosphate-dependent Rac exchange factor 1 (PREX1), cortactin binding protein 2 (CTTNBP2), doublesex and mab-3-related transcription factor-like family A1 (DMRTA1), and endothelin receptor type B (ENDRB). The invention also provides methods and compositions relating to enrichment of cells having thermogenic potential based on cell surface markers, e.g., CD29, identified as being predictive of such.

The present invention provides methods for identifying agents that increase lifespan and increase resistance to oxidative and / or electrophilic stress. Also provided are methods for identifying biomarkers of longevity or identifying pathways governing longevity in response to phosphatidylinositol 3,4,5-triphosphate signaling.

The present invention relates to a method of enhancing fruit ripening and stability and of delaying senescence in fruit and other plant tissues. This method consists of applying an effective amount of a lysophospholipid, such as lysophosphatidylethanolamine (18:1) (hereinafter referred to as LPE (18:1)) or lysophosphatidylinositol (hereinafter referred to as LPI) to the fruit and other plant tissues. Lysophospholipids such as LPE (18:1) and LPI were found to be superior to other lysophospholipids in delaying senescence and in inhibiting phospholipase D, a key enzyme in mediating membrane deterioration during of plant senescence. LPE (18:1) and LPI are naturally occurring and environmentally safe. Their use could replace many environmentally toxic compounds that are currently being used to retard senescence of flowers, fruits and leaves and to enhance fruit ripening.

The present invention relates to methods of treating Alzheimer's Disease which utilize agents that increase neuronal phosphotidylinositol 4,5-biphosphate (PIP2), and to differentiated stem cell-based assay systems that may be used to identify agents that modulate phosphoinositide levels and thereby treat a variety of diseases. It is based, at least in part, on the discovery that edelfosine, an agent that increases PIP2 levels by inhibiting an enzyme that catalyzes PIP2 breakdown, decreases levels of neurotoxic A&bgr;42 peptide, particularly in cells expressing a mutant presenilin gene associated with Familial Alzheimer's Disease.

The invention discloses a complete humanized antibody which is selected from humanized high-capacity phage antibody library and is high-affinity-combined with phosphatidylinositol proteoglycan 3. The invention includes a selection method of the antibody, an antibody coding sequence and corresponding amino acid residue sequence, and especially includes three CDR-zone sequences respectively at a heavy chain and a light chain, combination characters of an antigen and the construction method of the complete antibody. The antibody is a complete humanized antibody, is used for treatment in human body, is low in immunogenicity, is less in toxic and side effects, and has a potential value of treating liver cancer and melanin tumor.

This invention relates to novel 2,3-dihydroimidazo[1,2-c]quinazoline compounds, pharmaceutical compositions containing such compounds and the use of those compounds or compositions for phosphotidylinositol-3-kinase (PI3K) inhibition and treating diseases associated with phosphotidylinositol-3-kinase (PI3K) activity, in particular treating hyper-proliferative and / or angiogenesis disorders, as a sole agent or in combination with other active ingredients.

The invention discloses a breast cancer-related kinase mutation detection panel. The detection panel comprises receptor tyrosine kinase (RTK), phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase (MAPK) related genes, and an exon region and a part of intronic regions of a downstream gene. The invention further discloses a kit containing the detection panel. The detection panel can detect gene mutation guiding diagnosis and treatment more efficiently, is of great significance to clinical diagnosis and discovery of a target spot of target treatment, and can help lower gene detection cost of patients.

The invention relates to a method for preparing AS-605240 and an application thereof on medicines for treating inflammatory diseases. An improvement of the preparation method disclosed to the international patent is supplied to 5-quinoxaline methylene-2, 4-thiazolidinedione (AS-605240 with a structural formula I). 3, 4-diaminotoluene and glyoxal water solution as raw materials are relatively easy to obtain, reactive reagent, such as sodium bicarbonate, N-bromosuccinimide, carbon tetrachloride, and the like in each step is cheap and easy, and the reaction condition is mild. A great deal of mouse experimental curative effect observation of myocarditis, acute and chronic hepatitis, acute colitis and pancreatitis, which is induced by concanavalin A, is performed by the AS-605240, and the favorable curative effects of the AS-605240 are all confirmed. The prior TZDs, such as troglitazone, and the like are mainly used for aspects on treating diabetes mellitus, angiocardiopathy, and the like. In recent years, a study confirms that the AS-605240 protects the mouse joint and treats rheumatoid arthritis through restraining an osphatidylinositol 3 (PI3K) kinase gamma subtype signal way, therefore, the AS-605240 application on medicines for treating the inflammatory diseases opens up a new medical treatment field on the discovery of thiazolidinedione compound.

The invention provides a hepatocellular carcinoma vaccine targeting secondary lymphoid tissues. The vaccine comprises fusion protein comprising (a) phosphatidylinositol proteoglycan-3 (GPC3) and (b) lymphocyte chemotactic factor (XCL1) polypeptide of a specifically bonded chemokine receptor 1 (XCR1), nucleic acid encoding the fusion protein and vectors of the nucleic acid, wherein (a) is connectedwith (b) through a linker, and (a) lacks amino acid residues with a cell membrane anchoring effect. The vaccine comprises the fusion protein, the nucleic acid and / or the vectors, and application of the fusion protein, the nucleic acid and / or the expression vectors in prevention and treatment of liver cancers is provided. The vaccine has the effect of intervention of generation and development ofliver cancers, and can be applied to intervention of high-risk population of liver cancer, and for example, the vaccine can be applied to intervention of the generation progress of hepatitis B-relatedpatients to liver cancers.

The present invention relates to novel synthetic analogues of phosphatidyl-myo-inositol mannosides (hereinafter referred to as PIMs) of general formula (I): or a pharmaceutically acceptable salt thereof, to the method for preparing same and to the use thereof in the prevention or treatment of a disease associated with the overexpression of cytokines or of chemokines, in particular of TNF and / or of IL-12. The invention also relates to a pharmaceutical composition comprising at least one synthetic derivative of PIM.

The invention relate to a high-density sialic acid modified ibrutinib (IBR) nanocomposite and a preparation method thereof. The sialic acid modified IBR nanocomposites comprises IBR, phospholipid anda sialic acid derivative, wherein the molar ratio of IBR to phospholipid is 1:0.5 to 1:5, and the molar ratio of the sialic acid derivative to phospholipid is 1:19 to 1:1. The phospholipid is one or more of phosphatidylglycerol, phosphatidic acid, phosphatidylserine, phosphatidylinositol and cardiolipin. The nanocomposite can obviously improve the drug dissolution performance, provides an injectable product for reducing the daily dose of drugs, and can be used for clinical critical patients to solve the problem that the patients cannot take drugs orally. Based on the theory of ''immunopharmaceuticals'', the sialic acid is used to modify the composite, accumulation of the preparation in tumor site and the inhibitory effect on tumor microenvironment stromal cells are increased, so that the tumor therapeutic spectrum of IBR is expanded, and the drug efficacy is improved.

The invention relates to a fused ring compound and a preparation method, application and intermediate compound thereof. The fused ring compound can be used as an inhibitor of phosphatidylinositol 3-kinase.

The present invention relates to a pyrrolo[2,1-f][1,2,4]triazine compound, an isomer thereof or a pharmaceutically acceptable salt, ester or hydrate thereof, and a preparation method and application thereof. The pyrrolo[2,1-f][1,2,4]triazine compound has a structure expressed in general formula (I). The pyrrolo[2,1-f][1,2,4]triazine compound expressed in general formula (I) can inhibit a phosphatidylinositol-3 kinase (PI3K) signal pathway, thereby being used to prepare medicine for treating phosphatidylinositol-3 kinase related diseases such as cancer.

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.