38 results about "Ubiquitin-Specific Proteases" patented technology

The invention discloses a mutated ubiquitin specific protease 33 gene and application of the mutated ubiquitin specific protease 33 (USP33) gene to production of a medicine for treating colorectal cancer. A research finds out that KDM5B has high expression in a colorectal cancer clinical sample and a colorectal cancer cell line and promotes the proliferation of colorectal cancer cells through inhibiting USP33. A KDM5B inhibitor or a monoclonal antibody of the KDM5B can be used for remarkably inhibiting the proliferation of the colorectal cancer cells. A further research proves that the KDM5B is combined with a USP33 gene promotor region, and the inhibition of the expression to the USP33 gene is realized through combining an upstream specific regulation and control sequence GCACA / C or G / TGTGC. The mutated ubiquitin specific protease 33 gene obtained through a site-directed mutation PCR (Polymerase Chain Reaction) technology can be used for resisting the inhibition effect of the KDM58B, so that the growth of the colorectal cancer cell line is inhibited.

Provided are small molecule inhibitors of ubiquitin specific protease 2, 8 and 12 (USP2 and USP8 and USP12) activity and methods for their use in treating cancers. The small molecule inhibitors of the invention are particularly useful in the treatment of non-small cell lung cancers that are resistant to tyrosine kinase inhibitors and in the treatment of prostate cancer that is resistant to AR inhibitor therapy.

The present invention generally relates to 6-amino-2,4-dihydropyrano [2,3-c] pyrazoles as a ubiquitin specific protease 7 (USP7) inhibitor useful for the treatment of diseases mediated by malfunction of USP7, such as inflammation, cancer, and immunological disorders. The invention described herein also pertains to pharmaceutical compositions and methods for treating diseases mediated by malfunction of USP7, in mammals using compounds disclosed herein.

The invention provides a recombinant lentiviral vector containing ubiquitin-specific protease gene USP39-shRNA (short hairpin ribonucleic acid) and application thereof. The test proves that expression of USP39 in breast cancer tissue is obviously higher than that in normal breast tissue; the immunohistochemical detection confirms that the expression of USP39 in the breast cancer tissue is obviously higher than that in normal breast tissue; the immunohistochemical detection confirms that expression of USP39 protein in the breast cancer tissue is obviously higher than that in para-carcinoma tissue; siRNA (small interfering ribonucleic acid) is designed in a breast cancer cell system to interfere the expression of the USP39; it is found that proliferation of breast cancer cell after reducing the USP39 is obviously restrained; the cell apoptosis ratio is obviously improved; the cell ratio at the G1 stage is increased; the cell ratio at the S sage is reduced; and the clonality of the cell is obviously reduced. The test proves that the USP39 has an important role in facilitation of development of the breast cancer; and theoretical and experimental basis is provided for preparation of a drug for preventing and treating the breast cancer by the lentiviral vector containing USP39-shRNA.

The present invention concerns the identification of inhibitors of ubiquitin specific protease 7 (USP7), and methods of use thereof.

The present invention relates to USP47 (ubiquitin specific protease 47) inhibitors and methods for inducing apoptosis or cell death in a target cell. In certain embodiments, the invention relates to methods and kits to screen for related agents that induce apoptosis. Additionally, the invention relates to assays for screening compounds capable of acting as USP47 inhibitors.

A method of identifying a lead or candidate compound that modulates the activity of GTPase-Activating Protein SH3 Domain-Binding Proteins (G3BP) is provided, which includes determining whether a compound modulates the interaction between the N-terminal Nuclear Transport Factor 2-like (NTF2L) domain of G3BP and FGDF peptide of ubiquitin specific protease 10 (USP10) or non-structural protein 3 (nsP3).

The invention provides an application of USP 49 (ubiquitin-specific protease 49) in preparation of a drug for preventing or treating pancreatic ductal adenocarcinoma. An amino acid sequence of the USP 49 is represented as SEQ ID NO:1. The deubiquitinating enzyme USP49 interacting with FKBP5 protein is provided, a degradation and stabilization mechanism of the FKBP5 protein as well as molecular regulation for an FKBP5-AKT pathway by the deubiquitinating enzyme USP49 is determined, the function and the molecular mechanism of the pathway in the occurrence and development processes of pancreatic ductal adenocarcinoma are provided, new basis is provided for treatment of pancreatic ductal adenocarcinoma, and USP49 has direct guidance significance for personalized medical treatment of pancreatic ductal adenocarcinoma.

Provided are small molecule inhibitors of ubiquitin specific protease 2, 8 and 12 (USP2 and USP8 and USP12) activity and methods for their use in treating cancers. The small molecule inhibitors of the invention are particularly useful in the treatment of non-small cell lung cancers that are resistant to tyrosine kinase inhibitors and in the treatment of prostate cancer that is resistant to AR inhibitor therapy.

Inhibitors of ubiquitin specific protease 19 (USP19) of Formula (I) are provided, together with pharmaceutical compositions comprising said inhibitors, and methods of use thereof. The compounds can beused in in the treatment of muscular atrophy, obesity, insulin resistance or type II diabetes or in reducing the loss of muscle mass.

The present invention relates to USP47 (ubiquitin specific protease 47) inhibitors and methods for inducing apoptosis or cell death in a target cell. In certain embodiments, the invention relates to methods and kits to screen for related agents that induce apoptosis. Additionally, the invention relates to assays for screening compounds capable of acting as USP47 inhibitors.

The invention relates to a cholangiocarcinoma cell medicine target point. The medicine target point is ubiquitin specific protease 8, and the nucleotide sequence is shown as SEQID NO:1 in a sequence table. For the first time, the invention puts forward that USP8 is knocked down, so that proliferation, migration and invasion of cholangiocarcinoma cells can be notably restrained, MMP9 activity achieving important effects on cell adhesion, neoplasm invasiveness and transfer is reduced, and the USP8 is promoted to achieve effect of oncogene for growth and transfer ability of cholangiocarcinoma. New possibility is provided for development of cholangiocarcinoma medicines and cholangiocarcinoma prevention, treatment and prognosis.

The invention discloses a site-directed labelled ubiquitin-specific protease 7 and a preparation method and an application thereof. After site-directed mutation, the ubiquitin-specific protease 7 is subjected to site-directed labelling by non-natural amino acids with labelled groups, wherein the non-natural amino acids with the labelled groups are introduced by a tRNA synthetase / tRNA pair. The protein expression flow is optimized, and specific labels and expression vectors are selected; the non-natural amino acids are introduced through the tRNA synthetase and the tRNA pair. All the steps andthe conditions are in synergistic interaction, the protein expression quantity is improved and site-directed labelling is completed, and the preparation method is simple to operate and easy to promote, does not affect the structure and activity of the protease 7and has broad application prospects and great market value.

The present invention concerns the discovery of new selective inhibitors of ubiquitin specific proteases, their process of preparation and their therapeutic use.

The present invention relates to compounds of Formula (I) that are useful as inhibitors of the activity of the ubiquitin specific protease USP19. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in therapy.

The invention discloses a mutated ubiquitin specific protease 33 gene and application of the mutated ubiquitin specific protease 33 (USP33) gene to production of a medicine for treating colorectal cancer. A research finds out that KDM5B has high expression in a colorectal cancer clinical sample and a colorectal cancer cell line and promotes the proliferation of colorectal cancer cells through inhibiting USP33. A KDM5B inhibitor or a monoclonal antibody of the KDM5B can be used for remarkably inhibiting the proliferation of the colorectal cancer cells. A further research proves that the KDM5B is combined with a USP33 gene promotor region, and the inhibition of the expression to the USP33 gene is realized through combining an upstream specific regulation and control sequence GCACA / C or G / TGTGC. The mutated ubiquitin specific protease 33 gene obtained through a site-directed mutation PCR (Polymerase Chain Reaction) technology can be used for resisting the inhibition effect of the KDM58B, so that the growth of the colorectal cancer cell line is inhibited.

Provided are USP19 inhibitors, methods of treating obesity, metabolic syndrome and / or diabetes using the USP19 inhibitor compounds, as well as those compounds for use in methods of treating obesity, metabolic syndrome and / or diabetes. Also provided are methods of treating muscular atrophy, for example cachexia or sarcopenia with USP19 inhibitor compounds, plus those compounds for use in methods of treating muscular atrophy.

The present invention relates to compounds of Formula (I) that are useful as inhibitors of the activity of the ubiquitin specific protease USP19. The present invention also relates to pharmaceutical compositions comprising these compounds and to methods of using these compounds in therapy.

The invention belongs to the field of treatment of diseases and in particular relates to a deubiquitinating enzyme for stabilizing BMI1 in glioma. The deubiquitinating enzyme is ubiquitin-specific protease 22 (USP22) and the formation of a BMI1 level inhibition glioma transplanted tumor can be reduced through knocking down expression of the USP22.

Provided are USP19 inhibitors, methods of treating obesity, metabolic syndrome and / or diabetes using the USP19 inhibitor compounds, as well as those compounds for use in methods of treating obesity, metabolic syndrome and / or diabetes. Also provided are methods of treating muscular atrophy, for example cachexia or sarcopenia with USP19 inhibitor compounds, plus those a compounds for use in methods of treating muscular atrophy.

The present invention relates to USP47 (ubiquitin specific protease 47) inhibitors and methods for inducing apoptosis or cell death in a target cell. In certain embodiments, the invention relates to methods and kits to screen for related agents that induce apoptosis. Additionally, the invention relates to assays for screening compounds capable of acting as USP47 inhibitors.

Resistance of acute myeloid leukemia (AML) cells to DNA damaging therapeutic agents is dependent on CHK1 protein levels. Here, the inventors demonstrate that in AML, CHK1 protein stability relies on the expression and activity of Ubiquitin Specific Protease 7 (USP7). CHK1 and USP7 levels are positively correlated in AML cell lines and primary patient specimens with high CHK1 protein levels. USP7 associates with CHK1, leading to its stabilization by deubiquitinylation, and this association is enhanced in response to cytarabine treatment. Pharmacological or RNA interference-mediated inhibition of USP7 significantly reduced AML proliferation in vitro and in vivo, and increased AML cell death. It is important to note that USP7 inhibition synergized with cytarabine to kill AML cell lines. This is also the case in primary patient specimens with high CHK1 levels. Transcriptomic dataset analyses revealed that a USP7 gene signature is highly enriched in cells from AML patients at relapse, as well as in residual blasts from Patient Derived Xenograft (PDX) models treated with clinically relevant doses of cytarabine, strongly suggesting a relationship between USP7 expression and resistance to therapy. Finally, single cell analysis from AML patient at relapse versus diagnosis showed that a gene signature of the pre-existing subpopulation responsible for relapse is enriched in transcriptomes of patients with high USP7 level. Altogether, these data demonstrate that USP7 is a master regulator of CHK1 protein kinase in AML cells, and represents both a marker of resistance to chemotherapeutic treatments, as well as a potential therapeutic target to overcome treatment resistance.

The invention provides an application of USP 49 (ubiquitin-specific protease 49) in preparation of a drug for preventing or treating pancreatic ductal adenocarcinoma. An amino acid sequence of the USP 49 is represented as SEQ ID NO:1. The deubiquitinating enzyme USP49 interacting with FKBP5 protein is provided, a degradation and stabilization mechanism of the FKBP5 protein as well as molecular regulation for an FKBP5-AKT pathway by the deubiquitinating enzyme USP49 is determined, the function and the molecular mechanism of the pathway in the occurrence and development processes of pancreatic ductal adenocarcinoma are provided, new basis is provided for treatment of pancreatic ductal adenocarcinoma, and USP49 has direct guidance significance for personalized medical treatment of pancreatic ductal adenocarcinoma.

Inhibitors of ubiquitin specific protease 19 (USP19) of Formula (I) are provided, together with pharmaceutical compositions comprising said inhibitors, and methods of use thereof. The compounds can be used in in the treatment of muscular atrophy, obesity, insulin resistance or type II diabetes or in reducing the loss of muscle mass.

The invention provides a recombinant lentiviral vector containing ubiquitin-specific protease gene USP39-shRNA (short hairpin ribonucleic acid) and application thereof. The test proves that expression of USP39 in breast cancer tissue is obviously higher than that in normal breast tissue; the immunohistochemical detection confirms that the expression of USP39 in the breast cancer tissue is obviously higher than that in normal breast tissue; the immunohistochemical detection confirms that expression of USP39 protein in the breast cancer tissue is obviously higher than that in para-carcinoma tissue; siRNA (small interfering ribonucleic acid) is designed in a breast cancer cell system to interfere the expression of the USP39; it is found that proliferation of breast cancer cell after reducing the USP39 is obviously restrained; the cell apoptosis ratio is obviously improved; the cell ratio at the G1 stage is increased; the cell ratio at the S sage is reduced; and the clonality of the cell is obviously reduced. The test proves that the USP39 has an important role in facilitation of development of the breast cancer; and theoretical and experimental basis is provided for preparation of a drug for preventing and treating the breast cancer by the lentiviral vector containing USP39-shRNA.

The present invention concerns the identification of inhibitors of ubiquitin specific protease 7 (USP7), and methods of use thereof.