63 results about "Proteasome activity" patented technology

Methods for modulating proteasome activity in a subject is provided. Proteasome activity is modulated by administering a therapeutically effective amount of proteasome modulating pharmacological agent to a subject. In a preferred embodiment, the proteasome modulating pharmacological agent is a protease inhibitor. In another aspect, a screening assay for detecting and identifying proteasome modulating pharmacological agents to modulate proteasome activity in a subject is also provided.

A method to detect proteasome activity in permeabilized cells, and optionally in a multiplex assay to detect presence or amount of at least one molecule for a different enzyme-mediated reaction, is provided.

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention.

One aspect of the invention relates to inhibitors that preferentially inhibit immunoproteasome activity over constitutive proteasome activity. In certain embodiments, the invention relates to the treatment of immune related diseases, comprising administering a compound of the invention. In certain embodiments, the invention relates to the treatment of cancer, comprising administering a compound of the invention.

Proteinopathies result from the proteasome not acting efficiently enough to eliminate harmful proteins and prevent the formation of the pathogenic aggregates. As described herein, inhibition of proteasome-associated deubiquitinase Usp 14 results in increased proteasome efficiency. The present invention therefore provides novel compositions and methods for inhibition of Uspl4, enhancement of proteasome activity and treatment of proteinopathies.

The invention relates to a proteasome inhibitors and methods of using the same. The present invention provides boronic acid compounds, boronic esters, and compositions thereof that can modulate apoptosis such as by inhibition of proteasome activity. The compounds and compositions can be used in methods of inducing apoptosis and treating diseases such as cancer and other disorders associated directly of indirectly with proteasome activity.

We describe a method of detecting a therapeutic exosome, the method comprising detecting an activity of an exosome. The activity may be selected from the group consisting of: (a) immunodulatory activity; (b) complement inhibition activity; (c) proteasome activity; (d) glycolytic enzyme activity; (e) anti-oxidative activity; (f) extracellular matrix (ECM) modifying activity; (g) NT5E (CD73) ecto-5'-ectonucleotidase activity; (h) ion homeostasis activity; and (i) chaperone activity. If the exosome is detected as having one or more such activities, the exosome is likely to comprise a therapeutic exosome having therapeutic activity.

The present invention relates to a cosmetic and / or pharmaceutical active component for stimulating proteasome activity of skin cells comprising the broth obtained by inoculating a biomass of the algae, Gracilaria spp., particularly the algae, Gracilaria tikvahiae, with a yeast culture, and allowing fermentation of the biomass to produce a fermentation broth. Also described is a cosmetic and / or pharmaceutical active component for stimulating proteasome activity of skin cells comprising an extract of the algae, Gracilaria tikvahiae. The present invention also relates to topical compositions comprising as a a cosmetic and / or pharmaceutical active component a ferment of the algae, Gracilaria spp., particularly the algae, Gracilaria tikvahiae, or an extract of the algae, Gracilaria tikvahiae, or a combination of both.

The invention relates to a cDNA sequence, a coding protein, a full-length gene sequence and the clone method of a 26S proteinase body subunit RPT2 gene (DvRPT2)in Dunaliella viridis. The uplift expression of 26S proteinase body subunit RPT2 gene in Dunaliella viridis enhances the hydrolytic efficient of TP, accelerates that the substrate protein enters the active position of the proteinase body, reduces the abnormal protein content in the cell, and improves the salt resistance of Dunaliella viridis, so the research about Dunaliella viridis RPT2 subunit indicates the protein degradation pathway of 26S proteinase body, the salt endurance mechanism and the salt-resistance plant improvement, which has the finite theoretical and actual application value.

The present invention relates to tetranortriterpenoid compounds and pharmaceutical compositions thereof, which are provided for use in the treatment, diagnosis and / or prevention of trinucleotide repeat disorders (like a polyglutamine diseases, e.g Huntingdon's disease), amyloid diseases, neurodegenerative disease, protein misfolding diseases or tumors. The tetranortriterpenoid compounds of the present invention are further provided for the reduction and / or inhibition of the aggregation of amyloidogenic proteins, preferably of polyglutamine proteins (such as huntingtin) as well as for increasing proteasome activity. The present invention furthermore relates to nucleic acids, comprising the nucleotide sequences of two huntingtin fragments, as well as to cells and kits, which are useful in methods for assessing the aggregation of huntingtin and in methods for identifying compounds, which modulate the aggregation of huntingtin.

This inventions relates to compounds that inhibit the activity of the proteasome and both promotes hair growth and stimulates the production of hair follicles. The compounds provided herein are thus useful in stimulating hair growth, including hair density, in subject where this is desirable.

Improved regimens for administering proteasome inhibitors are described, wherein proteasome inhibition is more sustained relative to certain current regimens which permit substantial recovery of proteasome activity between doses of inhibitor.

The present invention concerns the use of compositions and methods of regulating or evaluating fertility in an animal, in particular a mammal. In various embodiments of the invention, methods of contraception include inhibiting proteasome activity of a gamete, in particular spermatozoon. Proteasomal activity may be inhibited in vitro or in vivo. Inhibitors of the proteasome pathway include, but are not limited to small molecules, peptides, polypeptides (e.g., antibodies and the like) and affinity reagents that bind various components of the proteasome pathway (e.g., aptamers, etc.). In some embodiments, the activity of the proteasome pathway or the activity of a component in the proteasome pathway is inhibited by antibodies that bind and inhibit one or more components of the proteasome pathway.

The invention discloses a bortezomib pharmaceutical composition and applications thereof, wherein the bortezomib pharmaceutical composition comprises, by weight, 0.1-200 parts of bortezomib, 0.1-500 parts of an auxiliary material for adjusting release rate, 0-10 parts of a small molecule adjusting agent, and 0-2000 parts of a pharmaceutically acceptable injectable solvent. According to the presentinvention, the bortezomib pharmaceutical composition has the controlled drug release behavior, and can maintain the effective blood concentration and the proteasome inhibition level in the body; through the long-acting injection of the bortezomib pharmaceutical composition, the in vivo blood concentration and the efficacy providing of bortezomib can be controlled, the treatment effect of the drugcan e improved, the acting time can be prolonged, and the toxic-side effect of the drug can be reduced; the in vivo proteasome inhibition pharmaceutical composition with characteristics of high efficiency, long acting and low toxic-side effect is provided; and the invention further discloses uses of the bortezomib pharmaceutical composition in treatment of refractory / recurrent multiple myeloma.

The present invention relates generally to novel allosteric regulators of proteasome activity, methods for preparation and use, and pharmaceutical compositions thereof. Specifically piperidine-2-carboxylic acid derivatives containing 1-oxo-aroyl group and a lipophilic ester side chain are disclosed as allosteric inhibitors of proteasome 2S activity, and as therapeutic agents for the treatment of proteasome-associated disorders in a subject.

The present invention relates to methods of treating Mycobacterium pathogen infection in a subject that involve: inhibiting proteasomal activity in a pathogen under conditions effective to make the pathogen susceptible to antibacterial host defenses; inhibiting enzyme activity in a pathogen under conditions effective to make the pathogen susceptible to antibacterial host defenses, where the enzyme is a DNA repair enzyme or a flavin-like co-factor synthesis enzyme, or inhibiting proteasomal and enzyme activity under conditions to make the pathogen susceptible to antibacterial host defenses. The present invention also relates to methods for screening compounds that inhibit proteasomal and protease activity, DNA repair enzyme activity, or flavin-like co-factor synthesis enzyme activity, where the inhibitory compounds have an ability to sensitize bacteria to the antibacterial effects of oxidative / nitrosative stress.

We describe a method of detecting a therapeutic exosome, the method comprising detecting an activity of an exosome. The activity may be selected from the group consisting of: (a) immunodulatory activity; (b) complement inhibition activity; (c) proteasome activity; (d) glycolytic enzyme activity; (e) anti-oxidative activity; (f) extracellular matrix (ECM) modifying activity; (g) NT5E (CD73) ecto-5'-ectonucleotidase activity; (h) ion homeostasis activity; and (i) chaperone activity. If the exosome is detected as having one or more such activities, the exosome is likely to comprise a therapeutic exosome having therapeutic activity.

A cancer treatment comprises the administration of a pro-drug compound identified by an in silico candidate identification screening. The pro-drug candidates are selected from a data base and calculations are carried out on the association of the pro-drug candidates to form a complex with a metal ion and a proteasome active site. The pro-drug inhibits the active site of the proteasome in the presence of the metal ion and has little or no effect in the absence of the metal ion. The pro-drug can be: 3,4-dihydroxybenzoic acid; galloflavin; 2-{[(carbamoylsulfanyl)acetyl]amino}benzoic acid; 6,7-Dihydroxycoumaranone; 3,6-bis(hydroxymethyl)pyridazin-4(1H)-one; and 4′,5,7-trihydroxyisoflavone, for binding with copper ion and proteasome.

The invention relates to an amino acid polypyridyl copper complex and a preparation method and application thereof. Chemical formulas are respectively [Cu(OH-PIP)(Phe)Cl] 3H2O (1), [Cu(OH-PIP)(Gly)(H2O)]NO3 2H2O (2), [Cu(OH-PIP)(Ala)(Cl)] (3), [Cu(OH-PIP)(Met)]n(PF6) 2H2O (4) and [Cu(OH-PIP)(Gln)(H2O)](Cl) 3H2O (5), wherein OH-PIP is 4-(1-hydro-imidazole[4,5-f][1,10]phenanthroline-2-xyl)phenol, Phe is phenylalanine, Gly is glycine, Met is methionine, Ala is alanine, and Gln is glutamine. After the anti-tumor activity of MCF-7, SMMC-7721, K562, A549 and SGC-7901 cells is evaluated by an MTT method, the amino acid polypyridyl copper complex is found to have the advantages that the good anti-cancer activity on the cells is good, the certain inhibiting function on the activity of proteasome is realized, and the amino acid polypyridyl copper complex can be used as a targeting anti-cancer drug with potential application value.

The invention relates to a protein deacetylase and proteasome double-target inhibitor, and a pharmaceutically acceptable salt, a stereoisomer, a preparation method and an application thereof. The compound is represented by general formula I, the compound has good histone deacetylase resisting activity, proteasome resisting activity and tumor cell proliferation resisting activity, and can be used for preparing medicines for preventing or treating related mammalian diseases caused by abnormal histone deacetylase expression or proteasome abnormality. The invention also relates to a pharmaceuticalapplication of a composition containing the compound with the structure of general formula I.

The invention discloses a sperm quality evaluation method, and belongs to the technical field of biological detection. According to the evaluation method, the proteasome activity in semen is taken as an index, the proteasome activity among different age groups, different sperm motility groups, different DNA fragment groups, different morphological rates and different head malformation rate groups is measured, the proteasome activity among different semen quality index groups is found to have no significant difference, but the higher the sperm proteasome activity expression is, the higher the sperm proteasome activity expression is, the higher the sperm proteasome activity expression is, the higher the sperm proteasome activity is. The fertilization rate and 2PN rate of conventional in-vitro fertilization are higher. Therefore, the sperm proteasome activity of a patient with unknown sterility or low conventional in-vitro fertilization rate can be considered and detected, and a basis is provided for clinically selecting conventional in-vitro fertilization or ICSI treatment.