117 results about "Cathepsin K" patented technology

Improved treatments of joint diseases, such as, e.g. osteoarthritis and rheumatoid arthritis, and pain, wherein a strontium-containing compound is administered alone or in combination with one or more second therapeutically and / or prophylactically active substances, selected from the group consisting of bisphosphonates, glucosamine, pallitative agents, analgesic agents, disease modifying anti-rheumatic compounds (DMARDs), selective estrogen receptor modulators (SERMs), aromatase inhibitors, non-steroidal anti-inflammatory agents (NSAIDs), COX-2 inhibitors, COX-3 inhibitors, opioids, inhibitors / antagonists of IL-1, inhibitors / antagonists of TNF-alpha, inhibitors of matrix metallo-proteinases (MMPs), cathepsin K inhibitors, inhibitors / antagonists of RANK-ligand, statins, glucocorticoids, chondroitin sulphate, NMDA receptor antagonists, inhibitors of interleukin-I converting enzyme, Calcitonin gene related peptide antagonists, glycine antagonists, vanilloid receptor antagonists, inhibitors of inducible nitric oxide synthetase (iNOS), N-acetylcholine receptor agonists, neurokinin antagonists, neuroleptic agents, PAR2 receptor antagonists and anabolic growth factors acting on joint tissue components. Pharmaceutical compositions comprising a strontium-containing compound and a second therapeutically and / or prophylactically active substance as defined above.

A novel cathepsin K crystalline stucture is identified. Also disclosed are methods of identifying inhibitors of this protease and methods of inhibiting cathepsin K using inhibitors with certain structural, physical and spatial characteristics.

This invention relates to a novel class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis.

This invention relates to class of compounds which are cysteine protease inhibitors, including but not limited to, inhibitors of cathepsins K, L, S and B. These compounds are useful for treating diseases in which inhibition of bone resorption is indicated, such as osteoporosis. They have the following structure: Formula (I)

The present invention relates to an agent for increasing BMD characterized by use of a cathepsin K inhibitor as a bone resorption inhibitor in combination with a type of PTH as a bone formation stimulator. This agent for increasing BMD is useful for the treatment of osteoporosis, bone fracture, arthritis, rheumatoid arthritis, osteoarthritis, hypercalcemia, osteometastasis of carcinoma, periodontal disease, bone Paget's disease and other bone metabolic diseases. For example, as the cathepsin K inhibitor, there can be mentioned a compound of formula (W) and a salt thereof, etc.

The present invention is directed to a method of using compounds of Formula (I) to inhibit Cathepsin B. Specifically the compounds of the present invention are useful as therapeutic agents for the treatment of tumor invasion, metastasis, Alzheimer's Disease, arthritis, inflammatory diseases such as chronic and acute pancreatitis, inflammatory airway disease, and bone and joint disorders, including osteoporosis, osteoarthritis, rheumatoid arthritis, psoriasis, and other autoimmune disorders, liver fibrosis, including liver fibrosis associated with HCV, all types of steatosis (including non-alcoholic steatohepatitis) and alcohol-associated steatohepatitis, non-alcoholic fatty liver disease, forms of pulmonary fibrosis including idiopathic pulmonary fibrosis, pathological diagnosis of interstitial pneumonia following lung biopsy, renal fibrosis, cardiac fibrosis, retinal angiogenesis and fibrosis / gliosis in the eye, schleroderma, and systemic sclerosis. The compounds of Formula (I) are also useful for treating subjects with both HCV and fibrosis in a mammal, particularly liver fibrosis, and subjects affirmatively diagnosed or at risk for both HCV and liver fibrosis.

The present invention provides a compound of the Formula:a pharmaceutically acceptable salt, a solvate, or a prodrug thereof, wherein m, n, Ar1, R1, R2, R3, R4, and R5 are those defined herein. The present invention also provides methods for using and preparing compounds of Formula I.

Compounds of the formula II:whereinR2 is the side chain of leucine, isoleucine, cyclohexylglycine, O-methyl threonine, 4-fluoroleucine or 3-methoxyvaline;R3 is H, methyl or F;Rq is trifluoromethyl and Rq′ is H or Rq and Rq′ define keto;Q is a p-(C1-C6alkylsulphonyl)phenyl- or an optionally substituted 4-(C1-C6alkyl)piperazin-1-yl-thiazol-4-yl- moiety have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

The invention relates to a kind of prenylflavonoids and their application in the preparation of anti-osteoporosis drugs. The invention isolated 7 prenylflavonoids from Jackfruit moraceae plants of the genus artocarpus (I) (Artocarpus / I) (I) (heterophyllus / I), were 5'HydroxycudraflavoneA, artochaminB, artelastoxanthone, artoindonesianinQ, kuwanonT, artoheteroidA and artoheteroidB. Activity tests showed that the prenylflavonoids of the invention has strong inhibitory activity on important therapeutic target for osteoporosis -- protease K, the prenylflavones' IC50 is 0.88 - 93.9mM, can be used for preparing drugs for treating osteoporosis.

Elevated levels of cathepsin E (catE) are demonstrated to be diagnostic of intestinal forms of cancer, such as colorectal cancer. Elevated levels of cathepsin E (catE, monomeric forms) are demonstrated to be detectable in the urine of animals having colorectal cancer, and a diagnostic / screening method for identifying and / or detecting colorectal cancer in an animal from a urine sample is provided. Specific tissue immunohistochemcial staining for catE (monomeric forms) in dysplastic tissue is also disclosed, and is shown to correlate with the level of dysplastic lesion severity. Hence, a method for identifying and determining the level of dysplastic lesion severity is provided. Cathepsin E mRNA transcription and expression levels are also demonstrated to be upregulated in dysplastic tissue, relative to non-dysplastic tissue. Hence, a method for transcriptionally profiling an animal to monitor the progression of colorectal disease is provided.

Compounds of the formula II:whereinR1 and R2 are independently H, F or CH3; orR1 forms an ethynyl bond and R2 is H or C3-C6 cycloalkyl which is optionally substituted with one or two substituents independently selected from methyl, CF3, OMe or halo;R3 is C1-C3 alkyl or C3-C6 cycloalkyl, either of which is optionally substituted with one or two methyl and / or a fluoro, trifluoromethyl or methoxy, when R3 is C3-C6 cycloalkyl it may alternatively be gem substituted with fluoro;R4 is methyl or fluoro; m is 0, 1 or 2;E is a bond, or thiazolyl, optionally substituted with methyl or fluoro;A1 is CH or N,A2 is CR6R7 or NR6, provided at least one of A1 and A2 comprises N;R6 is H, C1-C4 alkyl, C1-C4 haloalkyl, C1-C3 alkyl-O—C1-C3 alkyl, or when A2 is C, R6 can also be C1-C4alkoxy or F;R7 is H, C1-C4 alkyl or For a pharmaceutically acceptable salt, N-oxide or hydrate thereof, have utility in the treatment of disorders characterized by inappropriate expression or activation of cathepsin K, such as osteoporosis, osteoarthritis, rheumatoid arthritis or bone metastases.

This invention is directed to compound of Formula I and methods of using these compounds in the treatment of conditions in which modulation of a cathepsin, particularly cathepsin K or cathepsin L, will be therapeutically useful.

The invention discloses a serpin and a minimum functional fragment and immunosuppression effect thereof. The serpin SA from haemaphysalis longicornis has activity restraining effects on cathepsin B, cathepsin G, papain and blood coagulation X factors, a minimum functional fragment SA-RCL having the immunosuppression activity is determined and has restraining activity on the cathepsin G, the immunosuppression effects of the SA and the SA-CRL to immunocyte are verified, and the treatment effects of the SA and the SA-CRL in a mouse arthritis model are verified. In the manner, the preparation costof the SA is low, the minimum functional fragment SA-RCL is small in molecular weight, stable in nature, easy to absorb, poor in immunogenicity and not liable to neutralize and degrade by hosts, theSA and the SA-RCL can be used for development of vaccines for resisting tick-borne diseases and treatment of anti-inflammation diseases.

Compositions containing inhibitors of cathepsin K (CTSK) expression and / or activity are provided. Methods for the treatment of glaucoma using the compositions of the invention are further provided.