54 results about "Glutaminyl cyclase" patented technology

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.

An inhibitor of a glutaminyl peptide cyclotransferase, and use thereof for the treatment and/or prevention of a disease or disorder selected from the group consisting of inflammatory diseases selected from

• • a. neurodegenerative diseases, e.g. mild cognitive impairment (MCI), Alzheimer's disease, neurodegeneration in Down Syndrome, Familial British Dementia, Familial Danish Dementia, multiple sclerosis,
  • b. chronic and acute inflammations, e.g. rheumatoid arthritis, atherosclerosis, restenosis, pancreatitis,
  • c. fibrosis, e.g. lung fibrosis, liver fibrosis, renal fibrosis,
  • d. cancer, e.g. cancer/hemangioendothelioma proliferation, gastric carcinomas,
  • e. metabolic diseases, e.g. hypertension,
  • f. and other inflammatory diseases, e.g. neuropathic pain, graft rejection/graft failure/graft vasculopathy, HIV infections/AIDS, gestosis, tuberous sclerosis.

Additionally disclosed are a respective diagnostic method, assay and kit.

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 invention discloses a glutaminyl cyclase inhibitor. The structure of the glutaminyl cyclase inhibitor is shown in the following formula ( as shown in the description). The glutaminyl cyclase inhibitor (QC inhibitor) provided by the invention is designed according to the crystal structure of an active center of target pheron. The glutaminyl cyclase inhibitor shows favorable selectivity and specifity, and has higher druggability. The glutaminyl cyclase inhibitor is rich in parent structures, good in water solubility, good in transmembrane properties and high in activity.

Novel heterocyclic derivatives of formula (I):

or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein R^a, n, R¹ and R² are as defined herein, as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5).

Methods for the treatment and/or prevention of an inflammatory disease or disorder through administration of an inhibitor of a glutaminyl peptide cyclotransferase. Inflammatory diseases or disorders treated or prevented by methods disclosed herein include mild cognitive impairment (MCI), rheumatoid arthritis, atherosclerosis, restenosis, pancreatitis, sepsis and peritonitus. Further provided are respective diagnostic methods, assays and kits.

The present invention relates to novel glutaminyl-peptide cyclotransferase-like proteins (QPCTLs), which are isoenzymes of glutaminyl cyclase (QC, EC 2.3.2.5), and to isolated nucleic acids coding for these isoenzymes, all of which are useful for the discovery of new therapeutic agents, for measuring cyclase activity, and for determining the inhibitory activity of compounds against these glutaminyl cyclase isoenzymes.

A method of monitoring treatment of an inflammatory disease or an inflammatory associated disease with the use of the ratio of N-terminal pyroglutamate modified MCP-1 (MCP-1 N1pE):total concentration of MCP-1 within a biological sample as a biomarker, and a method for determining the proportion of N-terminal pyroglutamate modified MCP-1 in relation to the total concentration of MCP-1 in biological samples. Also disclosed are a diagnostic kit and a method for screening a glutaminyl cyclase (QC) inhibitor or measuring the effectiveness of a glutaminyl cyclase (QC) inhibitor.

The invention relates to a compound of formula (I): A-B-D-E (I) or a pharmaceutically acceptable salt, solvate or polymorph thereof, including all tautomers and stereoisomers thereof, wherein: A is selected from monocyclic and bicyclic heteroaryl, which may independently substituted by alkyl or amino; B is selected from alkyl, heteroalkyl, alkyl-amino, aryl, heteroaryl, cycloalkyl, heterocyclyl and alkylene, wherein said groups may independently be substituted by alkyl; D is selected from aryl-amino, heteroaryl-amino, cycloalkyl-amino, heterocyclyl, heterocyclyl-amino, urea, thioamide, thiourea, sulfonamide, sulfoximine and sulfamoyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups may independently be substituted; and E is selected from aryl, heteroaryl, cycloalkyl, heterocyclyl, wherein said aryl, heteroaryl, cycloalkyl and heterocyclyl groups may independently be substituted. The compounds of formula (I) are inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.

The invention relates to novel heterocyclic derivatives as inhibitors of glutaminyl cyclase (QC, EC 2.3.2.5). QC catalyzes the intramolecular cyclization of N-terminal glutamine residues into pyroglutamic acid (5-oxo-prolyl, pGlu*) under liberation of ammonia and the intramolecular cyclization of N-terminal glutamate residues into pyroglutamic acid under liberation of water.

The invention provides a glutamine acyl cyclase isoenzyme inhibitor as well as a preparation method and application thereof, the glutamine acyl cyclase isoenzyme inhibitor is a compound with a novel structural framework, and the preparation method of the novel inhibitor provided by the invention has the advantages that the raw materials are easy to obtain, and the preparation method is simple and feasible. According to the inhibitor provided by the invention, the molecular structure diversity of the glutamine acyl cyclase isoenzyme inhibitor is obviously expanded; the method can be widely applied to preparation of medicines for treating diseases related to high-specificity expression of the glutaminyl cyclase isoenzyme and preparation of kits for diagnosing the diseases related to high-specificity expression of the glutaminyl cyclase isoenzyme.

Benzimidazole compounds of formula (I), shown below, are disclosed. The compounds are potent human glutaminyl cyclase inhibitors. Also disclosed is a pharmaceutical composition containing one of these compounds and a pharmaceutical acceptable carrier, as well as a method of treating Alzheimer's disease or Huntington's disease by administering to a subject in need thereof an effective amount of such a compound.

The present invention relates to a vector for expressing a soluble glutaminyl cyclase (QC) containing a sequence encoding QC, a fusion protein tag upstream of the sequence encoding QC, and a linker having at least one (His)_x-tag between the sequence encoding QC and the fusion protein tag, wherein x is an integer of at least 6. Methods for expressing a soluble glutaminyl cyclase (QC) by the vector of the present invention are also provided.

The invention relates to the use of a compound of formula (I), or a composition containing the compound, as glutaminyl cyclase (QC) inhibitor and to methods of preparation.