199 results about "Protein tyrosine phosphatase" patented technology

This invention relates to compounds, compositions, and methods useful for modulating protein tyrosine phosphatase-1B (PTP-1B) 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 PTP-1B 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 PTP-1B genes. Such small nucleic acid molecules are useful, for example, for treating, preventing, inhibiting, or reducing obesity, insulin resistance, diabetes (eg. type II and type I diabetes) in a subject or organism, and for any other disease, trait, or condition that is related to or will respond to the levels of PTP-1B in a cell or tissue, alone or in combination with other treatments or therapies.

The present disclosure relates to compounds effective as human protein tyrosine phosphatase beta (HPTP-β) inhibitors thereby regulating angiogenesis. The present disclosure further relates to compositions comprising said human protein tyrosine phosphatase beta (HPTP-β) inhibitors, and to methods for regulating angiogenesis.

The present invention provides novel compounds of formula 1a, novel compositions, methods of their use, and methods of their manufacture, where such compounds are pharmacologically useful inhibitors of Protein Tyrosine Phosphatases (PTPase's) such as PTP1B, CD45, SHP-1, SHP-2, PTPα, LAR and HePTP or the like. The compounds are useful in the treatment of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance, obesity, immune dysfunctions including autoimmunity diseases with dysfunctions of the coagulation system, allergic diseases including asthma, osteoporosis, proliferative disorders including cancer and psoriasis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of / or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrenia, and infectious diseases.

Detection of expression of the provided phosphatases in cancers is useful as a diagnostic, for determining the effectiveness of drugs, and for determining patient prognosis. The encoded polypeptides further provide a target for screening pharmaceutical agents effective in inhibiting the growth or metastasis of tumor cells. The present invention further provides methods and compositions relating to agents that specifically bind to MKPX, PTP4A1, PTPN7, FEM-2, DKFZP66K0524 or FLJ20313 for treatment and visualization of tumors in patients.

The present invention provides novel compounds, novel compositions, methods of their use, and methods of their manufacture, where such compounds are pharmacologically useful inhibitors of Protein Tyrosine Phosphatases (PTPases) such as PTP1B, CD45, SHP-1, SHP-2, PTP alpha, LAR and HePTP or the like. The compounds are useful in the treatment of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance, obesity, immune dysfunctions including autoimmunity diseases with dysfunctions of the coagulation system, allergic diseases including asthma, osteoporosis, proliferative disorders including cancer and psoriasis, diseases with decreased or increased synthesis or effects of growth hormone, diseases with decreased or increased synthesis of hormones or cytokines that regulate the release of / or response to growth hormone, diseases of the brain including Alzheimer's disease and schizophrenia, and infectious diseases.

The present invention relates to a method of inhibiting growth of tumor cells which overexpress a receptor protein tyrosine phosphatase zeta (PTPζ) by treatment of the cells with antibodies which recognize PTPζ and / or inhibit PTPζ function. The present invention also provides compounds and pharmaceutically acceptable compositions for administration in the methods of the invention. The present invention also provides novel splice variants of protein PTPζ, PTPζ SM1 and PTPζ SM2. Nucleic acid probes specific for the spliced mRNA encoding these variants and affinity reagents specific for the novel proteins are also provided.

The present disclosure relates to compounds effective as human protein tyrosine phosphatase beta (HPTP-β) inhibitors thereby regulating angiogenesis. The present disclosure further relates to compositions comprising said human protein tyrosine phosphatase beta (HPTP-β) inhibitors, and to methods for regulating angiogenesis.

This invention relates to compounds, compositions, and methods useful for modulating protein tyrosine phosphatase type IVA (PRL3) 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 protein tyrosine phosphatase type IVA (PRL3) 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 (mRNA), and short hairpin RNA (shRNA) molecules and methods used to modulate the expression of protein tyrosine phosphatase type IVA (PRL3) genes.

Disclosed are novel compounds, novel compositions, methods of their use, and methods of their manufacture, where such compounds of Formula 1 are pharmacologically useful inhibitors of Protein Tyrosine Phosphatases (PTPases) such as PTP1B, CD45, SHP-1, SHP-2, PTPα, LAR and HePTP or the like, wherein n, m, X, Y, R1, R2, R3, R4, R5 and R6 are defined more fully in the description. The compounds are useful in the treatment of type I diabetes, type II diabetes, impaired glucose tolerance, insulin resistance, obesity, and other diseases.

Compositions and methods relating to small interfering RNA (siRNA) polynucleotides are provided as pertains to modulation of biological signal transduction. Shown are siRNA polynucleotides that interfere with expression of members of the protein tyrosine phosphatase (PTP) class of enzymes that mediate signal transduction, and with certain MAP kinase kinases (MKK). In certain preferred embodiments siRNA modulate signal transduction pathways comprising SHP2, cdc14a / b, cdc25A / B / C, KAP, PTP-ε, PRL-3, CD45, dual specificity phosphatase-3 (DSP-3), MKK-4, and / or MKK-7. Modulation of PTP-mediated biological signal transduction has uses in diseases associated with defects in cell proliferation, cell differentiation and / or cell survival, such as metabolic disorders (including diabetes and obesity), cancer, autoimmune disease, infectious and inflammatory disorders and other conditions. The invention also provides siRNA polynucleotides that interfere with expression of chemotherapeutic target polypeptides, such as DHFR, thymidylate synthetase, and topoisomerase I.

An application of the bromophenol compounds chosen from bis-(2,3-bibromo-4,5- dihydroxybenzyl)-ether, 2,2',3,3'-tetrabromo-4,4',5,5'-tetrahydroxydiphenyl methane, 2,2',3- tribromo-3',4,4',5-tetrahydroxy-6'-ethoxymethyl diphenylmethane, 3-bromo-4,5-bis-(2,3-dibromo -4,5-dihydroxybenzyl)-catechol, their pharmacologically acceptable derivatives, and their mixture in preparing the depressant of protein tyrosine phosphatase for treating diabetes and obesity is disclosed.

The present invention relates to the use of proteins which are differentially expressed in primary brain tumor tissues, as compared to normal brain tissues, as biomolecular targets for brain tumor treatment therapies. Specifically, the present invention relates to the use of immunotherapeutic and immunoimaging agents which specifically bind to one or more of human proteins angiopoietin related protein 2 (ARP-2,) secreted protein acidic, rich in cysteine (SPARC,) c-met proto-oncogene (C-MET,) brevican (BEHAB,) CD-44 antigen (CD-44,) tetraspanin 3 (TSPN3,) pleiotrophin (PTN,) osteopontin (OPN,) vasoactive intestinal peptide receptor-2 (VIPR-2,) and receptor protein tyrosine phosphatase zeta (PTPζ) for the treatment and visualization of brain tumors in patients. The present invention also provides compounds and pharmaceutically acceptable compositions for administration in the methods of the invention. The present invention also provides novel splice variants of protein PTPζ, PTPζ SM1 and PTPζ SM2. Nucleic acid probes specific for the spliced mRNA encoding these variants and affinity reagents specific for the novel proteins are also provided.

The invention discloses a combination marker used for liver cancer detection and application thereof. The combination marker used for liver cancer detection comprises the respective methylation levelsof adenylate kinase 055957 (AK055957), 3-hydroxybutyrate dehydrogenase 1 (BDH1), chromosome 6 open reading frame 223 (C6orf223), disabled homolog 2-interacting protein (DAB2IP), human coagulation factor XII (F12), Golgi reassembly stacking protein (GRASP), leucine-rich repeat-containing protein 4 (LRRC4), nuclear factor I / X (NFIX), 5-oxoprolinase (ATP-hydrolysing) (OPLAH), recombinant protein tyrosine phosphatase F interacting protein 1 (PPFIA1), Pleckstrin homology and SEC7 domain-containing protein 4 (PSD4) and T-box 15 (TBX15). Experiments prove that whether the genome DNA or plasma circulating free DNA (cfDNA) of to-be-detected liver tissue comes from patients with liver cancer or patients without liver cancer can be judged by detecting the combination marker, and accuracy is relatively high; and the combination marker has significant application value.

The invention provides an active fraction in a lucid ganoderma fruiting body, an extracting method, application thereof and a preparation. The activity half suppression ratio IC50 of the active fraction on protein tyrosine phosphatase-1B is below 80 mug / mL, and has a remarkable blood sugar reducing effect.

A compound of the formula (I): [0001]wherein X1 and X2 are the same or different and each is a bond or a spacer having 1 to 20 atom(s) in the main chain;[0002]one of R1 and R2 is a cycle group having substituent(s) selected from 1) an optionally substituted carboxy-C1-6 alkoxy group and 2) an optionally substituted carboxy-C1-6 aliphatic hydrocarbon group, wherein the cycle group optionally has additional substituent(s), and the other is an optionally substituted cycle group or a hydrogen atom; and[0003]R3, R4 and R5 are the same or different and each is a hydrogen atom or a substituent, or R4 may link together with R3 or R5 to form an optionally substituted ring;[0004]provided that when R3 is a hydrogen atom, R4 is a hydrogen atom and R5 is methyl, X2—R2 is not 4-cyclohexylphenyl; when R3 is 4-methoxyphenyl, R4 is a hydrogen atom and R5 is methyl, X2—R2 is not 4-methoxyphenyl; and when R1 or R2 is a hydrogen atom, the adjacent X1 or X2 is not a C1-7 alkylene;[0005]or a salt thereof exhibits a protein tyrosine phosphatase inhibitory action and is useful as a prophylactic or therapeutic agent for diabetes or the like.

The invention discloses a nucleic acid aptamer of protein tyrosine phosphatase SHP2 and a preparation method thereof, in particular relates to a nucleic acid and provides a nucleic acid aptamer of protein tyrosine phosphatase SHP2 with high specificity and high appetency and a preparation method and application thereof. The nucleic acid aptamer of the protein tyrosine phosphatase SHP2 has a parallel tetramer structure. The preparation method comprises the following steps: designing and synthesizing a single-chain DNA (deoxyribonucleic acid) random oligonucleotide library, screening a target oligonucleotide sequence, and identifying specificity and appetency of the target oligonucleotide sequence combined with target protein by a flow analysis method. The nucleic acid aptamer obtained by screening has the advantages of no toxicity, small molecular weight and good penetrability, can be synthesized and marked easily, only specifically recognizes SHP2 protein, does not have a recognition function on other homologous protein, and can be prepared into a potential inhibitor for selectively controlling the activity of the protein tyrosine phosphatase SHP2.

The present invention is related to the use of oxindole hydrazide derivatives of formula (I) for the treatment and / or prevention of metabolic disorders mediated by insulin resistance or hyperglycemia, comprising diabetes type I and / or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, obesity, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of oxindole hydrazide derivatives of formula (I) to modulate, notably to inhibit the activity of PTPs, in particular of PTP1B, TC-PTP, SHP and GLEPP-1. The present invention is furthermore related to novel oxindole hydrazide derivatives and method of preparation thereof.(I).

This invention relates to compounds, compositions, and methods useful for modulating protein tyrosine phosphatase-1B (PTP-1B) 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 PTP-1B 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 PTP-1B genes. Such small nucleic acid molecules are useful, for example, for treating, preventing, inhibiting, or reducing obesity, insulin resistance, diabetes (eg. type II and type I diabetes) in a subject or organism, and for any other disease, trait, or condition that is related to or will respond to the levels of PTP-1B in a cell or tissue, alone or in combination with other treatments or therapies.

Protein tyrosine phosphatase (PTP) Shp2 is a non-receptor PTP that involved in cell signaling and regulation of cell proliferation, differentiation, and migration. Shp2 mediates activation of kinases that are involved in the pathogenesis of human carcinoma. A high throughput screen identified compounds that inhibit the PTP Shp2. Several compounds were identified that selectively inhibit Shp2 over Shp1 with low to sub-micromolar activity. Also disclosed are methods of inhibiting a protein tyrosine phosphatase in a cell and treating cancer through selective inhibition of Shp2.

The present invention relates to a benzothiadiazole compound represented by the following formula I, and a preparation method and use thereof, the benzothiadiazole compound has the biological activityof inhibiting protein-tyrosine-phosphatase SHP2, can be used as a tool compound to study the biological functional relevance of the protein-tyrosine-phosphatase SHP2 in a cell signal transduction process, and provides a new means for prevention and treatment of cancer and metabolic and immune diseases.

The present invention provides compounds of Formula (I) and Formula (II) that are useful for modulating the biological activity of the protein tyrosine phosphatase-1b (PTP1B) enzyme. Compounds of this invention can be used to treat diseases and / or conditions in which the PTP1B enzyme is a factor. Such diseases and / or conditions include, but are not limited to, Type 1 diabetes, Type 2 diabetes, inadequate glucose tolerance, insulin resistance, obesity, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, low HDL levels, atherosclerosis, vascular restenosis, inflammatory bowel disease, pancreatitis, adipose cell tumors, adipose cell carcinoma, liposarcoma, dyslipidemia, cancer, and neurodegenerative diseases.

The present invention is related to substituted methylene amide derivatives of formula (I) and use thereof for the treatment and / or prevention of metabolic disorders mediated by insulin resistance or pyperglycemia, comprising diabetes type I and / or II, inadequate glucose tolerance, insulin resistance, hyperlipidemia, hypertriglyceridemia, hypercholesterolemia, obesity, polycystic ovary syndrome (PCOS). In particular, the present invention is related to the use of substituted methylene amide derivatives of formula (I) to modulate, notably to inhibit the activity of PTPs. Also the present invention relates to a method of treating diabetes type II, obesity and to regulate the appetite of mammals. The present invention is furthermore related to novel substituted methylene amide derivatives and method of preparation thereof. Formula (I).

The invention relates to a preparation method and applications of a sugar-reducing effective part of chicory. In the method, organic solvent extraction and macroporous resin separation and purification are adopted in crude chicory to obtain the sugar-reducing effective part, and the medical applications of the sugar-reducing effective part are illuminated. The preliminary activity screening test proves that the effective part obtained by the method provided by the invention has protein tyrosine phosphatase (PTP1B) inhibitor action, and the animal experiment proves that the effective part has the activity of reducing sugar and fat. The effective part can be used for preparing medicines or health products for treating diabetes, and can be used as a pharmaceutical composition.

The invention discloses a new application of theabrownin in the pharmaceutical field. The theabrownin of the invention is a natural product which uses black tea or pu'er tea as a raw material and is extracted from the tea. The result of pharmacological experiments indicates that the theabrownin has the function of markedly restraining protein tyrosine phosphatase. The theabrownin can also be used for preventing or curing II type diabetes, fat diabetes and adiposis. As the theabrownin is the natural product extracted from the black tea or pu'er tea, thus enjoying the advantages of no toxicity and side effect, safe and reliable use.

A novel gene (EPM2A) that is deleted or mutated in people with Lafora's disease is described. The EPM2A gene encodes a protein having an active catalytic site of a protein tyrosine phosphatase. Many different sequence mutations as well as several microdeletions in EPM2A have been found that co-segregate with Lafora's disease.

Provided are compounds capable of covalently binding to a protein tyrosine phosphatase (PTP). The compounds comprise Formula A: Also provided are compositions comprising one of the above compounds covalently bound to a member of the PTP superfamily, methods of labeling a PTP using the compounds, methods of isolating a PTP from a mixture of proteins using the compounds, methods of evaluating whether a substance is an inhibitor of a PTP using the compounds, methods of evaluating the specificity of an inhibitor of a PTP using the compounds, methods of identifying a PTP involved in a disease in a mammal using the compounds, and methods of diagnosing a disease in a mammal using the compounds.

The invention relates to a chickpea germ, effective part of bean sprout, a preparation method and application. The effective part of the total saponin and isoflavone can be obtained from the chickpea germ and bean sprout by adopting an alcohol extraction method or a water extraction method; the initial screening test of the effective part proves that: the effective part has the advantages of playing a role as an inhibitor for protein tyrosine phosphatase (PTP1B). The effective part can be used as a medicine for treating diabetes and as an application of health care product, simultaneously, the effective part or the derivative of which can be applied as a drug combination.

The present invention relates to protein tyrosine phosphatase (“PTPase”) inhibitors and their use with T cell activators in immunotherapy to treat cancer.