737 results about "Arrestin" patented technology

Compounds having the structure of formula I are described. The compounds can inhibit hepatitis C virus (HCV) replication, and in particular can inhibit the function of the HCV NS5A protein.

Oligonucleotide analogues conjugated to carrier peptides are provided. The disclosed compounds are useful for the treatment of various diseases, for example diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

Disclosed herein are in vitro assays for the identification of interactions between proteins or other molecules, the identification of transcriptional activator proteins, and the detection of compounds that inhibit protein / protein or protein / compound interactions. Also disclosed herein are in vitro assays for the selection of interacting proteins and transcriptional activator proteins out of libraries.

Cells are rendered sensitive to stimulation by introducing into a non-photoreceptor cell nucleic acid sequences encoding at least an opsin gene product, an arrestin gene product, and the alpha subunit of the heterotrimeric G protein of the Gq family. The introduced sequences are expressed by the cell to yield at least the opsin gene product, the arrestin gene product, and the alpha subunit of the heterotrimeric G protein of the Gq family. Retinal or a derivative thereof capable of bonding with the opsin gene product to form a rhodopsin is provided to the cell. The cell is then irradiated with light having a wavelength capable of converting the rhodopsin to metarhodopsin. The conversion of rhodopsin to metarhodopsin triggers a cascade of intracellular responses within the cell resulting in an increased intracellular concentration of IP3 and calcium ions.

There is provided a novel compound that inhibits interaction between murine double minute 2 (Mdm2) protein and p53 protein and exhibits anti-tumor activity. The present invention provides an imidazothiazole derivative represented by the following formula (1) having various substituents that inhibits interaction between Mdm2 protein and p53 protein and exhibits anti-tumor activity:wherein R1, R2, R3, R4, and R5 in the formula (1) each has the same meaning as defined in the specification.

The present invention relates to compounds, methods and pharmaceutical compositions for inhibiting proteases, particularly serine proteases, and more particularly HCV NS3 proteases. The compounds, and the compositions and methods that utilize them, can be used, either alone or in combination to inhibit viruses, particularly HCV virus.

A pharmaceutical comprising a therapeutic protein that binds to a therapeutic target, the protein being modified with a compound that inhibits binding of the protein to the therapeutic target, the modified protein being effective for reducing an immune response against the protein and for producing a therapeutic effect by binding to the therapeutic target. The therapeutic protein may be an antibody that includes an antibody combining site that binds to the therapeutic target.

Compositions and methods are provided for alleviating cancer in a mammal by administering a therapeutic dose of a pharmaceutical composition that inhibits activity of AXL protein activity, for example by competitive or non-competitive inhibition of the binding interaction between AXL and its ligand GAS6.

The present invention provides a drug for at least one of prevention and treatment of cardiac failure capable of suppressing cardiac depression and the onset of cardiac failure in ventricular remodeling, and a method for screening the drug. The drug for at least one of prevention and treatment of cardiac failure of the present invention contains a compound that inhibits a functional expression of ASK1 protein in a cardiomyocyte as an active ingredient, and a method for screening a drug for at least one of prevention and treatment of cardiac failure of the present invention includes selecting a medicinal component for at least one of prevention and treatment of cardiac failure from a drug candidate compound by using inhibition of a functional expression of ASK1 protein as an indication. As shown in FIG. 1, if ASK1 protein is removed, for example, the ventricle dilation can be attenuated in ventricular remodeling after myocardial infarction, pressure loading, or the like, which makes it possible to prevent and treat cardiac failure.

Compounds of the Formula and pharmaceutically acceptable salts thereof, wherein X1, X2, X3, X4, X5, X6, X7, R1, and Q1 are defined herein, inhibit protein kinase enzymes and are useful for the treatment and / or prevention of hyperproliferative diseases such as cancer, inflammation, psoriasis, allergy / asthma, disease and conditions of the immune system, disease and conditions of the central nervous system.

Compounds of formula (25) that inhibit protein kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.

Compounds that inhibit the activity of NF-κB or inhibit the activity of the proteasome or both promote bone formation and hair growth and are thus useful in treating osteoporosis, bone fracture or deficiency, primary or secondary hyperparathyrdidism, periodontal disease or defect, metastatic bone disease, osteolytic bone disease, post-plastic surgery, post-prosthetic joint surgery, and post-dental implantation; they also stimulate the production of hair follicles and are thus useful in stimulating hair growth, including hair density, in subject where this is desirable.

A pharmaceutical comprising a therapeutic protein that binds to a therapeutic target, the protein being modified with a compound that inhibits binding of the protein to the therapeutic target, the modified protein being effective for reducing an immune response against the protein and for producing a therapeutic effect by binding to the therapeutic target. The therapeutic protein may be an antibody that includes an antibody combining site that binds to the therapeutic target.

This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds, compositions and methods for the inhibition of kinase activity. The invention also provides compounds, compositions and methods for treating cell proliferative diseases and conditions.

The present invention relates to compounds of the following formula (I) and / or the pharmaceutically acceptable addition salts, solvates, enantiomers, diastereoisomers thereof, as well as mixtures thereof. The subject matter of the present invention thus also includes the preparation of compounds of formula (I), their uses, in particular in the inhibition of protein kinases which are implicated for example in numerous diseases such as cancers or immune system disorders.

The present invention relates to organic molecules capable of inhibiting protein tyrosine phosphatase activity. The invention further relates to the use of such molecules to modulate or regulate signal transduction by inhibiting protein tyrosine phosphatase activity. Finally, the invention relates to the use of such molecules to treat various disease states including diabetes mellitus.

This invention relates to compounds that inhibit protein tyrosine kinase activity. In particular the invention relates to compounds that inhibit the protein tyrosine kinase activity of growth factor receptors, resulting in the inhibition of receptor signaling, for example, the inhibition of VEGF receptor signaling and HGF receptor signaling. More particularly, the invention relates to compounds, compositions and methods for the inhibition of VEGF receptor signaling and HGF receptor signaling. The invention also provides compositions and methods for treating cell proliferative diseases and conditions.

The present invention provides a method for identifying inhibitors of protein kinases. Methods are also provided for inhibiting protein kinase activity. Specific non-peptide protein tyrosine kinase inhibitor are provided. The protein kinases produced using the method of the present invention may be used to treat a number of conditions in patients, including cancer, psoriasis, arthrosclerosis, or immune system activity.

Oligonucleotide analogues conjugated to carrier peptides are provided. The disclosed compounds are useful for the treatment of various diseases, for example diseases where inhibition of protein expression or correction of aberrant mRNA splice products produces beneficial therapeutic effects.

Methods for agents useful for treating asthma are disclosed. The methods include screening for agents that inhibit the production of a PKC-θ protein, as well as for agents that inhibit the kinase activity of a PKC-θ protein, or a functional fragment thereof, wherein such agents are useful for treating asthma. The methods also include screening for agents that inhibit the production of a reporter gene product encoded by a nucleic acid sequence operably linked to a PKC-θ promoter. Also disclosed are methods of treating asthma that include administering an agent that inhibits the production of a functional PKC-θ protein or the kinase activity of a PKC-θ protein or a functional fragment thereof. An isolated mast cell lacking expression of endogenous PKC-θ is also disclosed.

The present invention relates to compounds of the following formula (I) and / or the pharmaceutically acceptable addition salts, solvates, enantiomers, diastereoisomers thereof, as well as mixtures thereof. The subject matter of the present invention thus also includes the preparation of compounds of formula (I), their uses, in particular in the inhibition of protein kinases which are implicated for example in numerous diseases such as cancers or immune system disorders.

The present invention describes polynucleotides that have been discovered to correlate to the relative intrinsic sensitivity or resistance of cells, e.g., lung cell lines, to treatment with compounds that interact with and modulate, e.g., inhibit, protein tyrosine kinases, such as, for example, members of the Src family of tyrosine kinases, e.g., Src, Fgr, Fyn, Yes, Blk, Hck, Lck and Lyn, as well as other protein tyrosine kinases, including, Bcr-abl, Jak, PDGFR, c-kit and Ephr. These polynucleotides have been shown, through a weighted voting cross validation program, to have utility in predicting the resistance and sensitivity of lung cell lines to the compounds. The expression level of some polynucleotides is regulated by treatment with a particular protein tyrosine kinase inhibitor compound, thus indicating that these polynucleotides are involved in the protein tyrosine kinase signal transduction pathway, e.g., Src tyrosine kinase. Such polynucleotides, whose expression levels correlate highly with drug sensitivity or resistance and which are modulated by treatment with the compounds, comprise polynucleotide predictor or marker sets useful in methods of predicting drug response, and as prognostic or diagnostic indicators in disease management, particularly in those disease areas, e.g., lung cancer, in which signaling through the protein tyrosine kinase pathway, such as the Src tyrosine kinase pathway, is involved with the disease process.

The invention relates to the finding that the VHL tumour suppressor protein regulates hypoxia inducible factor alpha subunits, by targeting HIF alpha for destruction in normoxic, but not hypoxic cells. The invention provides assays for modulators of this interaction, and peptides based upon HIF alpha subunit sequence which may modulate this interaction.

A method of inhibiting angiogenesis in a mammal is disclosed, which employs a pharmaceutically acceptable composition containing a selective inhibitor of protein kinase CK2 (also known as casein kinase II) enzymatic activity, such as emodin, aloe-emodin, 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB), and 4,5,6,7-tetrabromobenzotriazole (TBB). Also disclosed is a use of a selective inhibitor of protein kinase CK2 enzymatic activity in the manufacture of a medicament for inhibiting angiogenesis. An in vitro method of screening a potential antiangiogenic agent is also disclosed. A kit for the treatment of a disease by inhibiting angiogenesis is disclosed that contains the pharmaceutically acceptable composition containing a selective inhibitor of protein kinase CK2 enzymatic activity.

This invention relates to the use of oligourea molecules to specifically inhibit protein-nucleic acid interactions. In particular, it provides an oligourea molecule that competes with the Tat molecule for the TAR RNA of HIV-1. Also provided is a method specifically inhibiting protein-nucleic and interactions, and kits.

In accordance with the invention, novel gene deletions and translocations involving chromosome 2 resulting in fusion proteins combining part of Anaplastic Lymphoma Kinase (ALK) kinase with part of a secondary protein have now been identified in human solid tumors, e.g. non-small cell lung carcinoma (NSCLC). Secondary proteins include Echinoderm Microtubule-Associated Protein-Like 4 (EML-4) and TRK-Fusion Gene (TFG). The EML4-ALK fusion protein, which retains ALK tyrosine kinase activity, was confirmed to drive the proliferation and survival of NSCLC characterized by this mutation. The invention therefore provides, in part, isolated polynucleotides and vectors encoding the disclosed mutant ALK kinase polypeptides, probes for detecting it, isolated mutant polypeptides, recombinant polypeptides, and reagents for detecting the fusion and truncated polypeptides. The disclosed identification of this new fusion protein enables new methods for determining the presence of these mutant ALK kinase polypeptides in a biological sample, methods for screening for compounds that inhibit the proteins, and methods for inhibiting the progression of a cancer characterized by the mutant polynucleotides or polypeptides, which are also provided by the invention.

Compounds that inhibit protein kinases such as Aurora-kinases and the VEGFR and PDGFR families of kinases, with an improved safety profile due to low CYP3A4 inhibition, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.

The present invention provides compounds having formula (I):wherein R′, R0, R1, X1, R2, R3, R3′, X2, X3 and R4 are as defined herein, and pharmaceutical compositions thereof. The present invention also provides methods of inhibiting proteases, more specifically aspartyl proteases. In certain embodiments, compounds inhibit BACE (β-site APP-cleaving enzyme), and thus are useful in the treatment or prevention of a disease characterized by β-amyloid deposits in the brain (including, but not limited to, Alzheimer's Disease). The present invention also provides methods for preparing compounds of the invention.