304 results about "Cyclase" patented technology

This inventions relates to compounds having the structure Formula Iand pharmaceutically acceptable salts thereof which are soluble guanylate cyclase activators. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.

A compound having the structureuseful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, angina pectoris, thromboses, restenoses, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver in a human or animal patient.

A compound of Formula (I): or a pharmaceutically acceptable salt thereof, are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The invention furthermore relates to processes for preparing compounds of Formula I, or a pharmaceutically acceptable salt thereof, for their use in the therapy and prophylaxis of the abovementioned diseases and for preparing pharmaceuticals for this purpose, and to pharmaceutical preparations which comprise compounds of Formula (I) or a pharmaceutically acceptable salt thereof.

A compound having the structureuseful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, angina pectoris, thromboses, restenoses, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver in a human or animal patient.

The invention relates to compounds having the structure of Formula (I) and pharmaceutically acceptable salts thereof, which are soluble guanylate cyclase activators. The compounds are capable of modulating the body's production of cyclic guanosine monophosphate (“cGMP”) and are generally suitable for the therapy and prophylaxis of diseases which are associated with a disturbed cGMP balance. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.

Compositions and related methods for treating IBS and other gastrointestinal disorders and conditions (e.g., gastrointestinal motility disorders, functional gastrointestinal disorders, gastroesophageal reflux disease (GERD), duodenogastric reflux, Crohn's disease, ulcerative colitis, inflammatory bowel disease, functional heartburn, dyspepsia (including functional dyspepsia or nonulcer dyspepsia), gastroparesis, chronic intestinal pseudo-obstruction (or colonic pseudoobstruction), and disorders and conditions associated with constipation, e.g., constipation associated with use of opiate pain killers, post-surgical constipation, and constipation associated with neuropathic disorders as well as other conditions and disorders are described. The compositions feature peptides that activate the guanylate cyclase C (GC-C) receptor.

The present methods and compositions are of use for treatment of conditions involving fibrosis, such as Peyronie's disease plaque, penile corporal fibrosis, penile veno-occlusive dysfunction, Dupuytren's disease nodules, vaginal fibrosis, clitoral fibrosis, female sexual arousal disorder, abnormal wound healing, keloid formation, general fibrosis of the kidney, bladder, prostate, skin, liver, lung, heart, intestines or any other localized or generalized fibrotic condition, vascular fibrosis, arterial intima hyperplasia, atherosclerosis, arteriosclerosis, restenosis, cardiac hypertrophy, hypertension or any condition characterized by excessive fibroblast or smooth muscle cell proliferation or deposition of collagen and extracellular matrix in the blood vessels and / or heart. In certain embodiments, the compositions may comprise a PDE-4 inhibitor, a PDE-5 inhibitor, a compound that elevates cGMP and / or PKG, a stimulator of guanylyl cyclase and / or PKG, a combination of a compound that elevates cGMP, PKG or NO with an antioxidant that decreases ROS, or a compound that increases MMP activity.

The invention provides novel guanylate cyclase-C agonist peptides and their use in the treatment of human diseases including gastrointestinal disorders, inflammation or cancer (e.g., a gastrointestinal cancer). The peptides can be administered either alone or in combination with an inhibitor of cGMP-dependent phosphodiesterase. The gastrointestinal disorder may be classified as either irritable bowel syndrome, constipation, or excessive acidity etc. The gastrointestinal disease may be classified as either inflammatory bowel disease or other GI condition, including Crohn's disease and ulcerative colitis, and cancer.

This inventions relates to compounds having the structure Formula I and pharmaceutically acceptable salts thereof which are soluble guanylate cyclase activators. The compounds are useful for treatment or prevention of cardiovascular diseases, endothelial dysfunction, diastolic dysfunction, atherosclerosis, hypertension, pulmonary hypertension, angina pectoris, thromboses, restenosis, myocardial infarction, strokes, cardiac insufficiency, pulmonary hypertonia, erectile dysfunction, asthma bronchiale, chronic kidney insufficiency, diabetes, or cirrhosis of the liver.

The present invention relates to novel inhibitors of glutaminyl cyclase and combinations thereof for the treatment of neuronal disorders, especially Alzheimer's disease, Down Syndrome, Parkinson disease, Chorea Huntington, pathogenic psychotic conditions, schizophrenia, impaired food intake, sleep-wakefulness, impaired homeostatic regulation of energy metabolism, impaired autonomic function, impaired hormonal balance, impaired regulation, body fluids, hypertension, fever, sleep dysregulation, anorexia, anxiety related disorders including depression, seizures including epilepsy, drug withdrawal and alcoholism, neurodegenerative disorders including cognitive dysfunction and dementia.

The present invention provides novel physiological substrates of mammalian glutaminyl cyclase (QC, EC 2.3.2.5), new effectors of QC, methods for screening for such effectors, and the use of such effectors and pharmaceutical compositions comprising such effectors for the treatment of conditions that can be treated by modulation of QC-activity. Preferred compositions additionally comprise inhibitors of DP IV or DP IV-like enzymes for the treatment or alleviation of conditions that can be treated by modulation of QC- and DP IV-activity.

Compositions and related methods for treating IBS and other gastrointestinal disorders and conditions (e.g., gastrointestinal motility disorders, functional gastrointestinal disorders, gastroesophageal reflux disease (GERD), duodenogastric reflux, Crohn's disease, ulcerative colitis, inflammatory bowel disease, functional heartburn, dyspepsia (including functional dyspepsia or nonulcer dyspepsia), gastroparesis, chronic intestinal pseudo-obstruction (or colonic pseudoobstruction), and disorders and conditions associated with constipation, e.g., constipation associated with use of opiate pain killers, post-surgical constipation, and constipation associated with neuropathic disorders as well as other conditions and disorders are described. The compositions feature peptides that activate the guanylate cyclase C (GC-C) receptor.

The present invention relates to the discovery of a novel molecular pathway involved in long-term hyperexcitability of sensory neurons, which, in higher animals, is associated with persistent pain. It is based on the discovery that, following injury to an axon of a neuron, an increase in nitric oxide synthase activity results in increased nitric oxide production, which, in turn, activates guanylyl cyclase, thereby increasing levels of cGMP. Increased cGMP results in activation of protein kinase G (“PKG”), which then is retrogradely transported along the axon to the neuron cell body, where it phosphorylates MAPKerk.

Methods of modulating type-I interferon production in a cell are provided. Aspects of the methods include modulating cytosolic cyclic di-adenosine monophosphate (c-di-AMP) activity in the cell in a manner sufficient to modulate type-I interferon production in the cell. Additional aspects of the invention include c-di-AMP activity modulatory compositions, e.g., c-di-AMP, mutant Listeria bacteria, cyclase and / or phosphodiesterase nucleic acid or protein compositions, etc. The subject methods and compositions find use in a variety of applications, including therapeutic applications.

This invention provides a new therapeutic or prophylactic agent for arthritis such as osteoarthritis. Specifically, it provides a therapeutic or prophylactic agent for arthritis such as osteoarthritis, or an agent for promoting the growth of articular chondrocyte, comprising a guanyl cyclase B (GC-B) activator as an active ingredient; or a method for inhibiting arthritis or for promoting the growth of articular chondrocyte by activating GC-B; or a method for screening an agent for promoting the growth of articular chondrocyte or an agent capable of treating arthritis using the GC-B activity as an indication.

Guanylin cyclase C compound of the inventions are disclosed. Conjugated compounds comprising guanylin cyclase C compound of the inventions conjugated to detectable or therapeutic moieties are disclosed. Methods of detecting, imaging and treating cancer and treating diarrhea are disclosed.

This invention also provides a method to prevent, control, and treata lipid metabolism disorder, a billary disorder, cardiovascular disease, obesity or an endocrine disorder by administering at least one agonist of guanalyte cyclase receptor either alone or in combination with a compound typically used to treat the disorder and or with an inhibitor of cGMP-dependent phosphodieasterases.

This invention provides a composition for increasing a body height of a patient with short stature or an individual other than patients with short stature. More specifically, the invention provides: a composition for increasing the body height of an individual comprising a guanyl cyclase B (GC-B) activator as an active ingredient, the composition being to be administered to an individual free from FGFR3 abnormality; a method for increasing the body height of an individual free from FGFR3 abnormality which comprises activating GC-B; a method for screening an agent for increasing the body height of an individual which comprises selecting an agent for increasing the body height using GC-B activity as an indication; and a method for extending a cartilage bone free from FGFR3 abnormality which comprises activating GC-B in an individual.

The invention at hand describes a method for the cyclization of peptides and proteins in which linear thioesters serve as substrates. The cyclization is catalyzed by thioesterase domains of NRPS or PKS cyclases. The substrates according to the present invention are composed of one linear peptide on which a charge-stabilized aromatic, heteroaromatic or araliphatic leaving group is bound. These substrates lead to higher yields and reaction rates than linear peptides able to be cyclized with methods known so far and, furthermore, allow the cyclization of such peptides which were previously not able to be cyclized.

This invention also provides a method to prevent, control, and treata lipid metabolism disorder, a biliary disorder, cardiovascular disease, obesity or an endocrine disorder by administering at least one agonist of guanalyte cyclase receptor either alone or in combination with a compound typically used to treat the disorder and or with an inhibitor of cGMP-dependent phosphodieasterases.

A unique carotenogenic biosynthetic gene cluster has been isolated from Panteoa agglomerans strain DC404, wherein the genetic organization of the cluster is crtE-idi-crtY-crtI-crtB-crtZ. The genes contained within this cluster encode geranylgeranyl pyrophosphate (GGPP) synthetase (CrtE), isopentenyl pyrophosphate isomerase (Idi), lycopene cyclase (CrtY), phytoene desaturase (CrtI), phytoene synthase (CrtB), and β-carotene hydroxylase (CrtZ). The gene cluster, genes and their products are useful for the conversion of farnesyl pyrophosphate to carotenoids. Vectors containing those DNA segments, host cells containing the vectors and methods for producing those enzymes by recombinant DNA technology in transformed host organisms are disclosed.

The present invention provides compounds having the formula: wherein A is a nitrogen-, oxygen-, or sulfur-linked aryl, alkyl, cyclic, or heterocyclic group, the group being further substituted with an electron contributing moiety; B is hydrogen, or a halogen, amino, or thiol group; C is hydrogen, or a halogen, amino, or thiol group; and D is a primary alcohol, a hydrogen, or an oxygen, nitrogen, carbon, or sulfur linked to phosphate, a phosphoryl group, a pyrophosphoryl group, or adenosine monophosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted phosphodiester bridge, or to adenosine diphosphate through a phosphodiester or carbon-, nitrogen-, or sulfur-substituted pyrophosphodiester bridge. The present invention also provides pharmaceutical compositions containing the above compounds, methods of using the above compounds as pharmaceuticals, and processes for preparing the above compounds. Also provided are methods for inhibiting an ADP-ribosyl transferase, ADP-ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme, and methods for treating a disease or condition associated with an ADP-ribosyl transferase, ADP-ribosyl cyclase, ADP-ribosyl hydrolase, or NAD-dependent deacetylase enzyme in a subject in need of treatment thereof.

The present invention is directed to compositions useful in treating or preventing ileus in a patient. The compositions of the invention include a pituitary adenylate cyclase activating peptide (PACAP) receptor antagonist and / or a vasoactive intestinal peptide (VIP) receptor antagonist in an amount sufficient to treat or prevent ileus in a patient. In one embodiment both a PACAP and VIP receptor antagonists are present, preferably in a combination that blocks vasoactive pituitary cyclase 1 (VPAC1), VPAC2 and pituitary adenylate cyclase 1 (PAC1) receptors. Methods of using such composition to treat or prevent ileus in a patient are also encompassed by the invention.

This invention also provides a method to prevent, control, and treat a lipid metabolism disorder, a billary disorder, cardiovascular disease, obesity or an endocrine disorder by administering at least one agonist of guanalyte cyclase receptor either alone or in combination with a compound typically used to treat the disorder and or with an inhibitor of cGMP-dependent phosphodieasterases.

The invention discloses a recombinant bacterium for producing beta-carotene as well as a construction method and application of the recombinant bacterium. The construction method comprises the following steps: respectively constructing superstrong gene expression modules of protein phytoene synthetase / lycopene cyclase coded by beta-carotene synthetic genes optimized by codons, phytoene dehydrogenase, protein geranyl diphosphate synthase coded by MAV (micro aerial vehicle) pathway genes and 3-hydroxy-3-methylglutaryl coenzyme A reductase; assembling the gene expression modules in vitro, so as to obtain four plasmids of the gene expression modules, integrating the plasmids into a host bacteria genome which does not produce beta-carotene and screening orange single colonies, so as to obtain the recombinant bacterium for producing beta-carotene. The recombinant bacterium disclosed by the invention is adopted for producing beta-carotene by fermental cultivation, and the yield of beta-carotene can reach 26.03mg / g DCW. Therefore, the recombinant bacterium has high performance of producing beta-carotene.

The present invention relates to the DNA sequence for eukaryotic genes encoding epsi cyclase isolated from romaine lettuce as well as vectors containing the same and hosts transformed with said vectors. The present invention provides methods for controlling the ratio of various carotenoids in a host and to the production of novel carotenoid pigments. The present invention also provides a method for treating disease by administering carotenoids obtained from transformed hosts, or by administering a composition containing the transformed hosts.

The present invention relates to the DNA sequence for eukaryotic genes encoding ε cyclase isolated from romaine lettuce as well as vectors containing the same and hosts transformed with said vectors. The present invention provides methods for controlling the ratio of various carotenoids in a host and to the production of novel carotenoid pigments. The present invention also provides a method for treating disease by administering carotenoids obtained from transformed hosts, or by administering a composition containing the transformed hosts.