42 results about "Deubiquitinating enzyme" patented technology

The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of conditions involving mitochondrial dysfunction and cancer. Compounds of the invention include compounds having the formula (II) or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R8, R9, R10, R12, Z, Y and m are as defined herein.

The invention designs and synthesizes a biaryl pyridine deubiquitinating enzyme inhibitor. The biaryl pyridine deubiquitinating enzyme inhibitor has the structure which is shown as a general formula (I). The biaryl pyridine deubiquitinating enzyme inhibitor provided by the invention has good inhibiting activity on deubiquitinating enzyme, and has a good in-vitro proliferation inhibiting effect ontumour cells, such as K562 cells, Hep-G2 cells, HCT-116 cells, WSD-DLCL cells and A549 cells. According to the compound disclosed by the invention, raw materials required for synthesis are easily obtained; a route design is reasonable; reaction conditions are mild; the yield in each step is high; the operation is simple and convenient; the biaryl pyridine deubiquitinating enzyme inhibitor is suitable for industrial production.

The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase L1 (UCHL1) and ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of cancer and conditions involving mitochondrial dysfunction. Compounds of the invention include compounds having the formula (I)or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as defined herein.

The invention provides application of a deubiquitinating enzyme inhibitor in preparation of a medicine for resisting rabies virus, and relates to the technical field of biological medicine. Experiments show that PR-619 has anti-rabies virus activity for the first time, and it is determined that PR-619 has prevention and treatment effects on rabies virus infection.

The present invention relates to novel compounds and method for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase L1 (UCHL1) and ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of cancer and conditions involving mitochondrial dysfunction. Compounds of the invention include compounds having the formula (I) or a pharmaceutically acceptable salt thereof, wherein R1, R2, R3, R4, R5, R6, R7, R8 and R9 are as defined herein.

The invention discloses an application of OTU Domain-Containing Deubiquitinase 1 in preparation of medicines for treating fatty liver and related diseases. According to the invention, a normal human hepatocyte L02 cell line is taken as a research object, lentivirus can be used for constructing an OTUD1 knockout and overexpression vector system, and an OTUD1 gene knockout or overexpressed L02 cellis obtained. The function of the OTUD1 gene in fatty degeneration is researched through a palmitic acid (PA) and oleic acid (OA) combination-induced fatty liver cell model. The result displays that under same PA+OA stimulation, compared with the L02 cell normally expressed by the OTUD1 gene, the red fat droplets in the L02 cell knockouted by the OTUD1 gene are large and multiple; and on the contrary, and the red fat droplets in the L02 cell overexpressed by the OTUD1 gene are small and less. The result shows that the OTUD1 gene can obviously inhibit liver lipid deposition and inhibit generation of fatty liver.

The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or Ubiquitin Specific Peptidase 30 (USP30). The invention further relates to the use of DUB inhibitors in the treatment of conditions involving mitochondrial dysfunction and cancer. Compounds of the invention include compounds having the formula (I): (I) or a pharmaceutically acceptable salt thereof, wherein R1a, R1b, R1c, R1d, R1e, R1f, R1g, R2, X, L and A are as defined herein.

The invention provides a drug for inhibiting the replication of Marek's disease virus, including deubiquitinase UL36 inhibitor, and a preventive or anti-Marek's disease drug. Through the experiment of inhibiting the enzyme activity encoded by the virus, the drug toxicity experiment at the CEF cell level, the virus CPE inhibition experiment and the chicken Marek's disease model experiment, the present invention screens out the ubiquitinase UL36 inhibitor DUBs‑IN‑1 and its derivatives for the first time It can not only inhibit the activity of UL36 at the enzyme level, inhibit the replication of Marek’s disease virus at the cell level, but also inhibit the growth of Marek’s disease tumors and visceral hemorrhage at the animal level, and has a strong effect and a small dose Advantages, it can be widely used as an anti-MD drug in the production practice of poultry industry to prevent Marek's disease.

The present invention relates to materials and methods for high throughput monitoring of target engagement of isopeptidases, such as deubiquitylating enzymes by, inter alia, small molecule inhibitors. In particular the invention relates to development of high throughput assays to measure isopeptidase activity in biological samples, such as cells, animal tissues, animal tumours, human tissue or patient-derived biopsies.

The present invention designs and synthesizes a class of biarylpyridine deubiquitinase inhibitors, which have the structure of general formula (I): Formula (I) The biarylpyridine deubiquitinase inhibitors provided by the present invention have Sutinase has good inhibitory activity, and has good in vitro proliferation inhibitory effect on tumor cells such as K562 cells, Hep‑G2 cells, HCT‑116 cells, WSD‑DLCL2 cells and A549 cells. The raw materials required for the synthesis of the compound of the invention are easily available, the route design is reasonable, the reaction conditions are mild, the yield of each step is high, the operation is simple and convenient, and the method is suitable for industrial production.

The invention discloses the function and application of the deubiquitinating enzyme ZRANB1 in regulating lipid metabolism. Application of inhibiting ZRANB1 gene expression in preparing a product having at least one function of treating and / or preventing obesity, promoting white fat cell burning, promoting weight loss, and inhibiting subcutaneous and / or intra-abdominal white fat accumulation / accumulation. The experiment of the present invention proves that ZRANB1, as a newly discovered important fat metabolism regulation molecule, can significantly reduce the white fat content of the body after its protein level is reduced. The discovery of the function of ZRANB1 will provide important scientific basis and application value for the prevention of obesity diseases and the treatment of weight loss.

The invention discloses the application of a substance that reduces the expression of USP1 in the preparation of a medicament for treating childhood T-lineage acute lymphoblastic leukemia. The invention discloses a short hairpin RNA forming a stem-loop structure, which is shRNA-1 or shRNA-2. The deubiquitinating enzyme USP1 has the functions of inhibiting cell apoptosis and promoting cell proliferation in T-line acute lymphoblastic leukemia cells. The present invention proves that inhibiting the expression of USP1 can promote the apoptosis of tumor cell leukemia cells and inhibit the proliferation of leukemia cells. The invention provides a new way for the treatment of T-line acute lymphoblastic leukemia, and the deubiquitinating enzyme USP1 is expected to become a potential target of anti-leukemia treatment, and has a very broad application prospect in the medical field.

The invention relates to a method for inhibiting the myogenic differentiation of bovine skeletal muscle satellite cells by interfering with the expression of UCH-L3, wherein the method is to suppress the myogenic differentiation of bovine skeletal muscle satellite cells by interfering with the expression of UCH-L3, wherein the The genome base sequence of UCH‑L3 is: SEQ NO.1. The method of the present invention regulates the myogenic differentiation process of bovine muscle satellite cells by changing the expression of UCH-L3, which can provide enlightenment for the research on deubiquitinating enzymes of muscle development and differentiation, and provide clinical research, diagnosis and treatment for muscle development and differentiation and injury repair Provide new ideas and references.

The invention discloses an application of OTU Domain-Containing Deubiquitinase 1 in preparation of medicines for treating fatty liver and related diseases. According to the invention, a normal human hepatocyte L02 cell line is taken as a research object, lentivirus can be used for constructing an OTUD1 knockout and overexpression vector system, and an OTUD1 gene knockout or overexpressed L02 cellis obtained. The function of the OTUD1 gene in fatty degeneration is researched through a palmitic acid (PA) and oleic acid (OA) combination-induced fatty liver cell model. The result displays that under same PA+OA stimulation, compared with the L02 cell normally expressed by the OTUD1 gene, the red fat droplets in the L02 cell knockouted by the OTUD1 gene are large and multiple; and on the contrary, and the red fat droplets in the L02 cell overexpressed by the OTUD1 gene are small and less. The result shows that the OTUD1 gene can obviously inhibit liver lipid deposition and inhibit generation of fatty liver.

The present invention relates to novel compounds and methods for the manufacture of inhibitors of deubiquitylating enzymes (DUBs). In particular, the invention relates to the inhibition of ubiquitin C-terminal hydrolase 30 or ubiquitin specific peptidase 30 (USP30). The novel compounds have formula (I): (Formula (I)) or are pharmaceutically acceptable salts thereof, wherein: R1a, R1b, R1c, R1d, R1e and R1f each independently represent hydrogen, optionally substituted C1-C6 alkyl or optionally substituted C3-C4 cycloalkyl, or R1b and R1c together form an optionally substituted C3-C6 cycloalkyl ring, or R1d and R1e together form an optionally substituted C3-C6 cycloalkyl ring; R2 represents hydrogen or optionally substituted C1-C6 alkyl; A represents an optionally further substituted 5 to 10 membered monocyclic or bicyclic heteroaryl, heterocyclyl or aryl ring; L represents a covalent bond or linker; B represents an optionally substituted 3 to 10 membered monocyclic or bicyclic heterocyclyl, heteroaryl, cycloalkyl or aryl ring; and when -A-L-B is at position x attachment to A is via a carbon ring atom of A, and either: A cannot be triazolopyridazinyl, triazolopyridinyl, imidazotriazinyl, imidazopyrazinyl or pyrrolopyrimidinyl; or B cannot be substituted with phenoxyl; or B cannot be cyclopentyl when L is an oxygen atom.

The invention discloses an ideal strain-type gene NPT1 capable of controlling stem coarseness, tillering number, seeds per ear, thousand seed weight and output and an application thereof. The NPT1 gene function and its expression quantity are closely related to the paddy rice stem coarseness, seeds per ear, seed weight and output, an elite allelic variation type npt1 obviously reduces the gene expression quantity, the paddy rice stem coarseness is increased, seeds per ear and seed weight are increased, and the output is increased. A further research found that NPT1 codes deubiquitinating enzyme analogous with human OTUB1 protein, by regulating and controlling OsSPL14 protein stability, the regulation and control of paddy rice strain (ear) type are realized. The npt1 and the regulation and control gene dep1-1 with excellent agronomic traits are polymerized, and the paddy rice output is increased. The NPT1 is taken as the novel gene for controlling important paddy rice agronomic traits, and the clone of the NPT1 provides certain theoretical support and technical support for paddy rice molecule pyramiding breeding and output improvement.