60 results about "Cathepsin S" patented technology

Substituted pyrazoles, methods of manufacturing them, compositions containing them, and methods of using them to treat, for example, autoimmune diseases or allergic conditions, including atopic allergic conditions, mediated by cathepsin S are described.

The present invention relates to a method for predicting the risk of a subject developing a cardiovascular event comprising detecting at least one biomarker in (a sample of) the cardiovascular system from said subject, wherein said biomarker comprises at least one protein selected from the group consisting of Tumor Necrosis Factor Alpha Precursor; Lysosomal-associated Membrane Protein (1); Interleukin-5 Precursor; Interleukin-6 Precursor; C-C Motif Chemokine (2) Precursor; C-C Motif Chemokine (5) Precursor RANTES; Cathepsin L1 Precursor; Adenylate Kinase (1); Leukotriene B4 Receptor (1); Complement Factor D; Secreted Phosphoprotein (1); Small Inducible Cytokine A17 Precursor; C-X-C Motif Chemokine (10) Precursor; Tumor Necrosis Factor Ligand Superfamily Member (11)(RANKL); C-C Motif Chemokine (18) Precursor; 72 kDa Type IVCollagenase Precursor; Neutrophil Collagenase Precursor; fatty acid binding protein (4); calpain (2), (m / II) large subunit; Macrophage Migration Inhibitory Factor; Cathepsin S Precursor; Interleukin (13) Precursor; and soluble ICAM-1.

Method of diagnosing persistent, chronic synovitis and progressive joint degradation in the joint of a mammal. The method including providing a test sample comprising synovial fluid, cell or tissue from the joint of a mammal; detecting the presence of bacterial DNA, measuring the concentration of one or more biomarkers being cathepsin K, MMP-2 and -9, cathepsin S, tartrate-resistant acid phosphatase, invariant chain, CD4+ T-lymphocytes, CD8+ T-lymphocytes, CD44+ mononuclear cells, Toll-like receptor-2, Toll-like receptor-9, or a combination thereof; and, comparing the concentration of the biomarker from the test sample to a corresponding biomarker concentration in a control sample from healthy dogs, or an internal PBMC control sample, wherein a statistically significant elevated concentration of the biomarker in the test sample indicates that the mammal's joint is diseased.

Disclosed are novel cathepsin S, K, F, L and B reversible inhibitory compounds of the formula (Ia) and (Ib) where R2, R3, R4, R5, R6, R7, R8, Het and X are defined herein. The compounds are useful for treating autoimmune and other diseases. Also disclosed are processes for making such novel compounds.

Cathepsin S is a highly active cysteine protease belonging to the papain superfamily. It is found mainly in lymph nodes, spleen, and macrophages and this limited occurrence suggests the potential involvement of this enzyme in the pathogenesis of degenerative disease. The invention relates to novel protease inhibitors, particularly inhibitors of the cysteine proteases of the papain superfamily and more particularly to Cathepsin S. The inhibitors are Furanone derivatives of Formula (II) which have a characteristic non-hydrogen substituent R5. They are selective over other members of the family and in particular show selectivity over other members of the Cathepsin family such as L and K.

Disclosed are novel cathepsin S, K, F, L and B reversible inhibitory compounds of the formulas (Ia) and (Ib) where R1, R2, R3, R4, R5, R6, R8, R9 and X are defined herein. The compounds are useful for treating autoimmune and other diseases. Also disclosed are processes for making such novel compounds

Disclosed are cathepsin S, K, F, L and B reversible inhibitory compounds of the formulas (Ia) and (Ib) where R2, R3, R4, R6, R8 and Y are defined herein. The compounds are useful for treating autoimmune and other diseases. Also disclosed are processes for making such novel compounds

The present invention relates to novel cathepsin S inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.

The present invention relates to novel selective cathepsin S inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.

The present invention is directed to compounds of formula I, below, that have the dual property of acting as cathepsin S inhibitors and of inhibiting HCV replication. Such compounds are therefore useful in treating disease states that include hepatitis C, Alzheimer's disease, and autoimmune disorders. The present invention is also directed to pharmaceutical compositions containing these compounds, and processes for preparing the compounds.

A method of inhibiting activity of a cathepsin L-like protease in cells or tissue and the use of the method in the treatment of disease such as cancer and inflammatory diseases is described. The method comprises administration of a cathepsin propeptide or a nucleic acid encoding a cathepsin propeptide. In particular embodiments, the propeptide is a Cathepsin S propeptide. Further, the use of propeptides having an Fc portion is described.

Novel inhibitors of cathepsin S, K, B, and L, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.

The present invention relates to novel selective cathepsin S inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.

The present invention is directed to methods of using compounds that are inhibitors of cysteine proteases, in particular, of both cathepsins S and K and optionally further cathepsins B and / or L in treating bone cancer. The present invention is directed to pharmaceutical compositions comprising these compounds for treating bone cancer and bone cancer pain, especially the pain associated with metastasis. A single compound can be used to ameliorate the pain, the injury to bone, while also reducing tumor growth, the risk of metastasis and / or invasiveness of the cancer.

The present invention relates to an amidopyridinol derivative or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition including an amidopyridinol derivative or a pharmaceutically acceptable salt thereof as an active component. An amidopyridinol derivative represented by Chemical Formula 1 or a pharmaceutically acceptable salt thereof has an excellent antiangiogenic effect in a chorioallantoic membrane model, and thus is useful as an agent for preventing or treating diseases associated with angiogenesis, such as macular degeneration or arthritis, and also has an excellent colitis-inhibitory effect in a model of inflammatory bowel diseases, and thus is useful as an agent for preventing or treating inflammatory bowel diseases. Upon inoculation of lung cancer cells in a chorioallantoic membrane model, the amidopyridinol derivative of Chemical Formula 1 or the pharmaceutically acceptable salt thereof inhibits angiogenesis and tumor growth that are caused by tumorigenesis, and also inhibits the activity of cathepsin S that plays an important role in metastasis and invasion of cancer, and thus is useful as an inhibitor of cancer growth and metastasis.

This invention relates 4-amino-azepan-3-ones of formula (I) which are useful as protease inhibitors, particularly of cathepsin S, and as such are useful for preventing a number of diseases amongst which are atherosclerotic lesions and pulmonary diseases such as asthma and allergic reactions.

The present invention concerns methods of using Cathepsin S inhibitors and compounds of Formula I that are inhibitors of cathepsin S in treating CNS disorders, diseases, and injuries, particularly neurodegenerative conditions. The present invention is directed to pharmaceutical compositions comprising these compounds for treating CNS disorders.

Novel inhibitors of cathepsin S, K, B, and L, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.

The invention relates to a method of inhibiting chemotherapy induced upregulation of Cathepsin S on the surface of tumour cells, the method comprising the administration of a Cathepsin S inhibitor to said cells. Also provided is a therapy comprising an anti Cathepsin S antibody, in particular an anti-Cathepsin S antibody which does not inhibit the proteolytic effect of Cathepsin S but nevertheless inhibits angiogenesis and a combination treatment comprising a Cathepsin S inhibitor and a therapeutic agent.

The invention provides a pseudosciaena crocea Cystatin recombinant protein and application thereof, and belongs to the technical field of gene engineering. The pichia pastoris engineering bacterium for efficiently expressing the pseudosciaena crocea Cystatin recombinant protein is constructed and is preserved in the China Center for Type Culture Collection, and the preservation number is CCTCC NO:M 2020369. The pseudosciaena crocea Cystatin recombinant protein produced by using pichia pastoris engineering bacteria can inhibit the activity of papain, pseudosciaena crocea cathepsin B and pseudosciaena crocea cathepsin S, up-regulate the expression level of inflammation-related factors TNF alpha in macrophages, and induce the generation of an antibacterial active substance nitric oxide in the macrophages; and therefore, the pseudosciaena crocea Cystatin recombinant protein has a good application prospect as a protease inhibitor and an immunopotentiator.

The invention relates to a method for separating and purifying cathepsin L. The method comprises the following steps: dissociating out the cathepsin from crude enzyme liquid of the cathepsin L by thermal treatment, eliminating influence of other enzymes with thermal instability, and then centrifuging to obtain a crude enzyme; eliminating other cathepsin such as cathepsin B, cathepsin H, cathepsin S and the like, the property of which is similar with the cathepsin L by hydrophobic gelchromatography and ion-exchange column chromatography, collecting components with enzymatic activity and then precipitating by 70% of ammonium sulfate; re-dissolving the obtained precipitate by a buffer solution and dissociating the cathepsin L from a complex formed by the cathepsin L and a natural inhibitor thereof at the same time, removing a low molecular weight enzyme inhibitor through ultrafiltration and purification and then concentrating target enzyme; and finally carrying out size-exclusion chromatography and efficient liquid-phase separation on the obtained concentrated solution to obtain the cathepsin L. The cathepsin L (CL) obtained by the method has high purity and better activity maintenance.

A method of inhibiting angiogenesis in a group of cells, a tissue or an organ includes administering an antibody molecule or nucleic acid encoding an antibody molecule to the cells, tissue or organ, wherein the antibody molecule specifically binds cathepsin S, but does not inhibit proteolytic activity of cathepsin S.

This invention relates to peptidyl compounds of the formulas (I) and (II) active as cathepsin S, a cysteine protease, inhibitors. The compounds are selective, reversible inhibitors of the cathepsin S are therefore useful in the treatment of autoimmune and other diseases. The invention also relates to processes for preparing such compounds and pharmaceutical compositions comprising them.

Cathepsin S is a highly active cysteine protease belonging to the papain superfamily. It is found mainly in lymph nodes, spleen, and macrophages and this limited occurrence suggests the potential involvement of this enzyme in the pathogenesis of degenerative disease. The invention relates to novel protease inhibitors, particularly inhibitors of the cysteine proteases of the papain superfamily and more particularly to Cathepsin S. The inhibitors are Furanone derivatives of Formula (II) which have a characteristic non-hydrogen substituent R5. They are selective over other members of the family and in particular show selectivity over other members of the Cathepsin family such as L and K.

The present invention relates to a method for monitoring the effect of in vivo administration of Cathepsin S inhibitors by measuring accumulation of an intermediate degradation product of invariant chain (Ii), in particular the p10 Ii fragment, in blood of dosed subjects.

Use of cathepsin S inhibitors for the treatment of an allergic condition, in particular an atopic allergic condition, more specifically for the treatment of hay fever, asthma, atopic dermatitis or a food allergy.

The present invention relates to novel selective cathepsin S inhibitors, the pharmaceutically acceptable salts and N-oxides thereof, their uses as therapeutic agents and the methods of their making.

A first aspect of the invention relates to a compound of formula (I), or a pharmaceutically acceptable salt, hydrate, complex or pro-drug thereof,wherein:one of R3 and R4 is H, and the other is selected from C1-6-alkyl, C1-6-haloalkyl, C1-6-alkoxy, and C6-12-aralkyl;or R3 and R4 are each independently selected from C1-6-alkyl and halo;R9 is a substituted 5 or 6-membered aryl or heteroaryl group or a 6,5- or 6,6-fused biaryl or heterobiaryl group.Compounds of formula (I) exhibit surprisingly high efficacies for human cathepsin S, excellent selectivity verses other mammalian cathepsins and are useful for treatment of diseases such as rheumatoid arthritis, multiple sclerosis, myasthenia gravis, transplant rejection, diabetes, Sjogrens syndrome, Grave's disease, systemic lupus erythematosis, osteoarthritis, psoriasis, idiopathic thrombocytopenic purpura, allergic rhinitis, asthma, atherosclerosis, obesity, chronic obstructive pulmonary disease and chronic pain.