120 results about "Phosphatase inhibitor" patented technology

Novel indole and azaindole compounds of the following structure and their use as fructose-1,6-bisphosphatase inhibitors is described: and pharmaceutically acceptable prodrugs and salts thereof.

The invention provides methods and compositions for modulating the sensitivity of cells to cytotoxic compounds and other active agents. In accordance with the invention, compositions are provided comprising combinations of ectophosphatase inhibitors and active agents. Active agents include antibiotics, fungicides, herbicides, insecticides, chemotherapeutic agents, and plant growth regulators. By increasing the efficacy of active agents, the invention allows use of compositions with lowered concentrations of active ingredients.

A collection container and a method for collecting a biological sample, particularly whole blood, includes at least one stabilizing agent in an amount effective to stabilize and inhibit protein degradation and / or fragmentation. The stabilizing agent is able to stabilize proteases in the biological sample, particularly at the point of collection, by inhibiting protein degradation and / or fragmentation in the sample when the sample is stored. The stabilizing agent comprises or consists of one or more protease inhibitors.

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 disclosure provides compositions and methods for the treatment of ocular conditions associated with angiogenesis, comprising administering a nucleic acid that encodes for a tyrosine phosphatase suppressor to a subject.

A method of treating SHP-2 phosphatase associated diseases in a subject includes administering a SHP-2 inhibitor to the subject.

The present invention provides a method for identifying inhibitors of protein kinases and / or protein phosphatases. Methods are also provided for inhibiting protein kinase and / or protein phosphatase activity. Specific non-peptide protein tyrosine kinase and / or protein phosphatase inhibitors are provided. The protein kinase or protein phosphatase inhibitors of the present invention may be used to treat a number of conditions in patients, including cancer, psoriasis, arthrosclerosis, immune system activity, Type II diabetes, and obesity.

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, e.g., to a composition that, at room temperature, when contacted with a sample comprising phosphoproteins, can fix and stabilize cellular phosphoproteins, preserve cellular morphology, and allow the sample to be frozen to generate a cryostat frozen section suitable for molecular analysis. The composition comprises (1) a fixative that is effective to fix the phosphoproteins, and that has a sufficient water content to be soluble for a stabilizer and / or a permeability enhancing agent); (2) a stabilizer, comprising (a) a kinase inhibitor and (b) a phosphatase inhibitor and, optionally, (c) a protease (e.g., proteinase) inhibitor; and (3) a permeability enhancing agent (e.g. PEG). Methods are described for preserving phosphoproteins, using such a composition. Also described are endogenous surrogate markers for monitoring protein degradation, including the loss of posttranslational modifications (such as phosphorylation), e.g. the following removal of a cell or tissue from a subject; and exogenous molecular sentinels (e.g. phosphoproteins attached to magnetic nanoparticles) that allow one to evaluate the processing history of a cellular or tissue population sample.

This invention relates to a process of synthesis and composition of open chain (ring), closed ring, linear branched and or substituted polyamines, polyamine derived tyrosine phosphatase inhibitors and PPAR partial agonists / partial antagonists via a series of substitution reactions and optimizing the bioavailability and biological activities of the compounds. Polyamines prevent the toxicty of neutoxins and diabetogenic toxins including paraquat, methyphenyl pyridine radical, rotenone, diazoxide, streptozotocin and alloxan. These polyamines can be to treat neurological, cardiovascular, endocrine acquired and inherited mitochondrial DNA damage diseases and other disorders in mammalian subjects, and more specifically to the therapy of Parkinson's disease, Alzheimer's disease, Lou Gehrig's disease, Binswanger's disease, Olivopontine Cerebellar Degeneration, Lewy Body disease, Diabetes, Stroke, Atherosclerosis, Myocardial Ischemia, Cardiomyopathy, Nephropathy, Ischemia, Glaucoma, Presbycussis, Cancer, Osteoporosis, Rheumatoid Arthritis, Inflammatory Bowel Disease, Multiple Sclerosis and as Antidotes to Toxin Exposure.

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.

Novel FBPase inhibitors of the formula I are useful in the treatment of diabetes and other conditions associated with elevated blood glucose.

The present invention discloses a screening method of a compound for inhibiting mycobacterium tuberculosis. The method comprises the following steps: (1) establishing a screening model adopting tyrosine phosphatase as a target point: adopting genome DNA of tubercle bacillus H37 Rv as a template, adopting a PCR technology to clone tyrosine phosphatase gene, transforming host cells, culturing the transformant to obtain recombinant tyrosine phosphatase from the culture, carrying out enzyme activity analysis, and establishing the screening model adopting tyrosine phosphatase as the target point; and (2) adopting the screening model established in the step (1) to screen a compound providing inhibition activity for the tyrosine phosphatase. With the method of the present invention, the tyrosine phosphatase inhibitor with anti-mycobacterium tuberculosis effect can be rapidly and efficiently screened. In addition, the present invention further discloses a compound screened by using the screening method, and uses of the compound in preparations of drugs for treatments of diseases, wherein the inducement or one of the inducements of the diseases is the tyrosine phosphatase.

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 present invention provides a method of inhibiting protein phosphatase 2A (PP2A) in a human subject in need thereof comprising administering to the subject an amount of from 0.1 mg / m2 to 5 mg / m2 of a compound having the structureor a salt, zwitterion, or ester thereof, so as to thereby inhibit protein phosphatase 2A (PP2A) in the subject.

A method for measuring an analyte in a whole blood sample comprising the steps of (1) bringing the whole blood sample into contact with a first substance which is carried on an insoluble carrier and specifically binds to the analyte to be measured and a second substance which is labeled with an alkaline phosphatase and specifically binds to the analyte to be measured, and (2) measuring a resulting complex on the basis of an enzyme reaction of the alkaline phosphatase, the measuring step (2) being carried out in the presence of an inhibitor of endogenous alkaline phosphatases, is disclosed.

The invention concerns RAC-PK and fragments thereof, as well as activators and inhibitors of RAC-PK for use as medicaments, particularly in the treatment of diseases concerned with abnormalities in processes modulated by insulin, such as cellular proliferation, insulin deficiency and / or excess blood sugar levels. Moreover, the invention provides RAC-PK for use in screening potential mimics or modulators thereof. A method for screening for agents capable of affecting the activity of GSK3 is also disclosed. The invention further provides a screening kit comprising the RAC-PK as an active principle, and a method for screening compounds which are candidate mimics or modulators of RAC-PK activity comprising detecting specific interactions between the candidate compounds and RAC-PK. There is also provided a process for activating RAC-PK comprising treatment thereof with a phosphatase inhibitor.

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.

Disclosed are compounds of the Formula Iand pharmaceutically acceptable salts and prodrugs thereof, wherein A, B; R1, R2, R3, R4 and R5 are as defined in the specification.Such compounds are tyrosine phosphatase inhibitors and useful in the treatment or prevention of Type II Diabetes Mellitus. Also encompassed by the invention are formulations comprising the noted compounds, processes for preparing such compounds, a method for treating or preventing Type II Diabetes Mellitus.

The present invention provides, inter alia, methods for treating or ameliorating the effects of a glioma. Methods of this invention include administering to a subject in need thereof an effective amount of a first active agent, such as e.g., an angiotensin receptor blocker, an antifungal agent, a bisphosphonate, an oxytocin inhibitor, an interleukin-1 (IL-1) inhibitor, a cyclooxygenase inhibitor, an α2δ voltage-dependent calcium channel (VDCC) inhibitor, a dihydroorotate dehydrogenase inhibitor, a calcium channel blocker, a renal sodium-chloride symporter inhibitor, an a2 adrenergic agonist, a phenothiazine antipsychotic, a calcineurin inhibitor, a 5-HT agonist, an angiotensin-converting enzyme (ACE) inhibitor, a direct rennin inhibitor, or combinations thereof, and a second active agent, which is a chemotherapeutic agent. Compositions for treating or ameliorating the effects of a glioma are also provided.

The present invention provides modulators of β-catenin phosphorylation. More specifically, the present invention provides inhibitors and enhancers of β-catenin Serine 45 (S45) phosphorylation. Examples of inhibitors provided by the invention are the proteins Dishevelled (Dvl), Wnt, phosphatase PP2A and CKI7. Examples of enhancers of beta-catenin phosphorylation are phosphatase inhibitors and proteins that promote β-catenin acetylation, like FRAT1. In addition, the present invention provides compositions and uses of the modulators of the invention, specifically for the treatment of cancer, as well as a method for screening such modulators.

The present invention relates to methods for modulating the growth of tumor and pathogen cells and the resistance of cells to foreign compounds, i.e. drugs, antibiotics, etc. by altering the ATP gradient across biological membranes. The altering of the ATP gradient across biological membranes is achieved through the manipulation of ecto-phosphatase activity and ABC transporter molecule activity which may also be useful to confer herbicide resistance to plants, confer antibiotic resistance to bacteria, confer drug resistance to yeast cells, or to reduce resistance in cells to facilitate chemotherapeutic treatments, and to reduce resistance in bacteria and yeast. The present invention is also directed to the methods for identifying ecto-phosphatase inhibitors and uses thereof.

Expression of a phosphatase inhibitor in heart cells can be used to treat cardiac disorders, e.g., heart failure. Decreasing phosphatase activity can improve β-adrenergic responsiveness.

The present invention provides a method for identifying inhibitors of protein kinases and / or protein phosphatases. Methods are also provided for inhibiting protein kinase and / or protein phosphatase activity. Specific non-peptide protein tyrosine kinase and / or protein phosphatase inhibitors are provided. The protein kinase or protein phosphatase inhibitors of the present invention may be used to treat a number of conditions in patients, including cancer, psoriasis, arthrosclerosis, immune system activity, Type II diabetes, and obesity.

The invention provides an application of compounds Pyrrocidines in preparation of an anti-tuberculosis drug, namely, an application of the compounds Pyrrocidines, derivatives of the compound Pyrrocidines or pharmaceutically acceptable salts of the compounds Pyrrocidines as tyrosine phosphatase inhibitors or in preparation of the tyrosine phosphatase inhibitors. The compounds 19-O-methyl-pyrrrocidine B and pyrrrocidine B have inhibitory activity on mycobacterium tuberculosis tyrosine phosphatase B, and IC50 of the compounds is 3.9 mu M and 75.5 mu M respectively. The compounds can effectively inhibit dephosphorylation activity of the mycobacterium tuberculosis tyrosine phosphatase B and has the clinical application potential for tuberculosis treatment; besides, the compounds Pyrrocidines are natural-metabolism active micro-molecular products separated from microorganisms and can be produced through chemical synthesis and large-scale fermentation separation, the sources are abundant, the production cost is low, and the possibility of medicine preparation is high.