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75 results about "Proteasome degradation" patented technology
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Proteasomes are part of a major mechanism by which cells regulate the concentration of particular proteins and degrade misfolded proteins. Proteins are tagged for degradation with a small protein called ubiquitin. The tagging reaction is catalyzed by enzymes called ubiquitin ligases.
Treatment of protein degradation disorders
ActiveUS20060239909A1Augmenting protein stressReduce sensitivityCompounds screening/testingBiocideProteasome degradationCompound (substance)
The invention relates to methods of treating protein degradation disorders, such cellular proliferative disorders (e.g., cancer) and protein deposition disorders (e.g., neurodegenerative disorders). The invention provides methods and pharmaceutical compositions for treating these diseases using aggresome inhibitors or combinations of aggresome inhibitors and proteasome inhibitors. The invention further relates to methods and pharmaceutical compositions for treating multiple myeloma. New HDAC / TDAC inhibitors and aggresome inhibitors are also provided as well as synthetic methodologies for preparing these compounds.
Owner:DANA FARBER CANCER INST INC +1
Compounds acting at the centrosome
InactiveUS20060167106A1Network disruptionBiocideBacterial antigen ingredientsActin cytoskeletonProteasome degradation
The present invention relates to compounds, and methods utilizing compounds, which exhibit one or more of the following properties: i) disrupts organization of an actin cytoskeleton of a cell; ii) disrupts organization of a microtubule network of a cell; iii) induces accumulation of tubulin at centrosomes but does not induce accumulation of tubulin in a nucleus of a cell; iv) induces accumulation of tubulin at centrosomes at a concentration of 500 nM or less within four hours; v) induces accumulation of Hsp70 and has weak-to-moderate proteasome inhibitory activity; and vi) does not have proteasome inhibitory activity when assayed on purified proteasomes.
Owner:SYNTA PHARMA CORP
Composition for enzyme inhibition
ActiveUS20060128611A1SolubilityImprove solubilityAntibacterial agentsOrganic active ingredientsSolubilityProteasome degradation
Compositions comprising one or more practically insoluble proteasome inhibitors and a cyclodextrin, particularly a substituted cyclodextrin, substantially increase the solubility of these proteasome inhibitors and facilitate their administration. Such compositions optionally comprise a buffer. Methods of treatment using such compositions are also disclosed.
Owner:ONYX THERAPEUTICS
Compounds for enzyme inhibition
InactiveUS20070105786A1Inhibiting and reducing HIV infectionAffecting levelBiocideNervous disorderEnzyme inhibitionAziridine
Peptide-based compounds including heteroatom-containing, three-membered rings efficiently and selectively inhibit specific activities of N-terminal nucleophile (Ntn) hydrolases associated with the proteasome. The peptide-based compounds include an epoxide or aziridine, and functionalization at the N-terminus. Among other therapeutic utilities, the peptide-based compounds are expected to display anti-inflammatory properties and inhibition of cell proliferation. Oral administration of these peptide-based proteasome inhibitors is possible due to their bioavailability profiles
Owner:ONYX THERAPEUTICS
Epitope synchronization in antigen presenting cells
InactiveUS20050130920A1Stimulate discovery and clinical developmentEasy to acceptImmunoglobulin superfamilyGenetic material ingredientsEpitopeCancer cell
Disclosed herein are vaccines and methods for inducing an immune response against cancer cells and cells infected with intracellular parasites. Vaccines having housekeeping epitopes are disclosed. The housekeeping epitope is formed by housekeeping proteasomes in peripheral cells, but not by professional antigen presenting cells. A vaccine containing a housekeeping epitope that is derived from an antigen associated with a peripheral target cell can thus direct an immune response against the target cell. Methods of treatment are also disclosed, which involve administering a vaccine having a housekeeping epitope.
Owner:MANNKIND CORP
Methods and compositions for treating cancer using proteasome inhibitors
ActiveUS20050267037A1Restore sensitivityAvoid stress responseBiocideCell receptors/surface-antigens/surface-determinantsCancer cellProteasome degradation
The present invention relates to therapeutic compositions for treating cancer or preventing the growth of cancer cells, e.g., tumor growth, in a subject. The present invention also relates to methods for treating cancer, e.g., inhibiting tumor growth, in a subject who has become resistant to treatment, by administering to a subject an effective amount of a proteasome inhibitor and an effective amount of a therapeutic agent, e.g., a chemotherapeutic agent. The present invention further relates to methods for purging bone marrow, i.e., removing cancer cells from bone marrow, by exposing the bone marrow cells to a proteasome inhibitor and a therapeutic agent, e.g., a chemotherapeutic agent.
Owner:DANA FARBER CANCER INST INC
Method of epitope discovery
A method of epitope discovery comprising the step of selecting an epitope from a population of peptide fragments of an antigen associated with a target cell, wherein the fragments have a known or predicted affinity for a major histocompatibility complex class I receptor peptide binding cleft, wherein the epitope selected corresponds to a proteasome cleavage product of the target cell.
Owner:MANNKIND CORP
Selective proteasome inhibitors for treating diabetes
InactiveUS20100240581A1Treat and prevent diabetesChronic inflammationBiocideAntipyreticProteasome degradationProteasome inhibitor
Methods of modulating chronic low-grade inflammation are provided. More particularly, methods of treating diabetes, such as for example, type-2 diabetes mellitus, in a mammal by administering an effective amount of a selective proteasome inhibitor are provided. Also provided are unit dosage forms of such inhibitors.
Owner:THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
Markers for colorectal cancer
InactiveUS20060188883A1Reduce and eliminate biological activityReduce expressionMicrobiological testing/measurementDisease diagnosisCancer cellBifunctional
Provided are previously uncharacterised markers of cancers, for example colorectal cancers, and uses of these as diagnostic and prognostic markers of cancers, and in particular colorectal cancers. The markers are SEQ ID NO: 1—hnRNP-K; SEQ ID NO:2—HMG-1; SEQ ID NO:3—proteasome subunit alpha type 1; SEQ ID NO:4—bifunctional purine biosynthesis protein; SEQ ID NO:5—ST11; SEQ ID NO:6—annex in IV; SEQ ID NO:7—60 kDa heat shock protein; SEQ ID NO:8—T complex protein 1 beta subunit; SEQ ID NO:9—T complex protein 1 epsilon subunit; SEQ ID NO: 10—mortalin; and SEQ ID NO: 11—TER-ATPase. The invention further provides related methods and materials for the use of the markers in therapeutic intervention in colorectal and other cancers e.g. to specifically target neoplastic cells without causing significant toxicity in healthy tissues, and to provide methods for the evaluation of the ability of candidate therapeutic compounds to modulate the biological activity of cancerous cells from the colon, rectum and other tissues.
Owner:AUVATION +2
Method of treating CD30 positive lymphomas
InactiveUS20060177442A1Good curative effectSuppress NF-kB activationBiocideDipeptide ingredientsProteasome degradationAntibody
Methods for treating lymphomas characterized by expression of CD30 using anti-CD30 antibodies and proteasome inhibitors in combination are disclosed.
Owner:MEDAREX LLC
Methods for identifying inhibitors
Vif binds to APOBEC3G and induces its rapid degradation, thus eliminating it from cells and preventing its incorporation into HIV-1 virions. Vif contains two domains, one that binds APOBEC3G and another with a conserved SLQ(Y / F)LA motif that mediates APOBEC3G degradation by a proteasome-dependent pathway. Provided herein are methods of exploiting these discoveries to develop compounds useful to inhibit Vif degradation of APOBEC3G, and thereby inhibit viral infection and / or replication.
Owner:OREGON HEALTH & SCI UNIV
Cell-based luminogenic and nonluminogenic proteasome assays
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.
Owner:PROMEGA
Analogs of Salinosporamide A
Disclosed herein are analogs of Salinosporamide A, having the Formulae Ia-IVa as follows: Like Salinosporamide A, the compounds of the present invention will inhibit the proteasome, an intracellular enzyme complex that destroys proteins the cell no longer needs. Without the proteasome, proteins would build up and clog cellular machinery. Fast-growing cancer cells make especially heavy use of the proteasome, so thwarting its action is a compelling drug strategy.
Owner:PRESIDENT & FELLOWS OF HARVARD COLLEGE
Epitope synchronization in antigen presenting cells
InactiveUS20070184062A1Stimulate discovery and clinical developmentEasy to acceptImmunoglobulin superfamilyCancer antigen ingredientsEpitopeCancer cell
Owner:MANNKIND CORP
Methods and compositions useful for treating diseases involving bcl-2 family proteins with isoquinoline and quinoline derivatives
InactiveUS20160038503A1BiocideBoron compound active ingredientsAbnormal tissue growthAutoimmune condition
The present invention relates to a compositions for and methods for cancer treatment, for example, hematopoietic cancers (e.g. B-cell Lymphoma). In other aspects, the invention provides methods for treating particular types of hematopoietic cancers, such as B-cell lymphoma, using a combination of one or more of the disclosed compounds and, for example, 26S proteasome inhibitors, such as, for example, Bortezomib. In another aspect the present invention relates to autoimmune treatment with the disclosed compounds. In another aspect, this invention relates to methods for identifying compounds, for example, compounds of the BH3 mimic class, that have unique in vitro properties that predict in vivo efficacy against B-cell lymphoma tumors and other cancers as well as autoimmune disease.
Owner:EUTROPICS PHARMA
Alpha-keto carbonyl calpain inhibitors
InactiveUS20060258598A1Maintain good propertiesSenses disorderNervous disorderCathepsin HPercent Diameter Stenosis
The present invention relates to novel α-keto carbonyl calpain inhibitors for the treatment of neurodegenerative diseases and neuromuscular diseases including Duchenne Muscular Dystrophy, Becker Muscular Dystrophy and other muscular dystrophies. Disuse atrophy and general muscle wasting can also be treated. Diseases of the eye, in particular cataract, can be treated as well. Generally all conditions where elevated levels of calpains are involved can be treated. The compounds of the invention may also inhibit other thiol proteases such as cathepsin B, cathepsin H, cathepsin L, papain or the like. Multicatalytic Protease (MCP) also known as proteasome may also be inhibited and the compounds can therefore be used to treat cell proliferative diseases such as cancer, psoriasis, and restenosis. The compounds of the present invention are also inhibitors of cell damage by oxidative stress through free radicals and can be used to treat mitochondrial disorders and neurodegenerative diseases, where elevated levels of oxidative stress are involved.
Owner:SANTHERA PHARMA SCHWEIZ
Epitope synchronization in antigen presenting cells
Disclosed herein are vaccines and methods for inducing an immune response against cancer cells and cells infected with intracellular parasites. Vaccines having housekeeping epitopes are disclosed. The housekeeping epitope is formed by housekeeping proteasomes in peripheral cells, but not by professional antigen presenting cells. A vaccine containing a housekeeping epitope that is derived from an antigen associated with a peripheral target cell can thus direct an immune response against the target cell. Methods of treatment are also disclosed, which involve administering a vaccine having a housekeeping epitope.
Owner:MANNKIND CORP
Medical devices with proteasome inhibitors for the treatment of restenosis
Methods, compositions and devices for inhibiting restenosis are provided. Specifically, proteasome inhibitor compositions and medical devices useful for the site specific delivery of proteasome inhibitors are disclosed. In one embodiment the medical device is a vascular stent coated with a proteasome inhibitor selected from the group consisting of a boronic acid, a C-terminal peptide aldehyde and derivatives and analogues thereof. In another embodiment an injection catheter for delivery an anti-restenotic effective amount of proteasome inhibitor to the adventitia is provided.
Owner:MEDTRONIC VASCULAR INC
Proteasome inhibitors and uses thereof
ActiveUS20180282317A1High selectivityNervous disorderOrganic chemistryImmunologic disordersProteasome degradation
The compounds of the present invention are represented by the following compounds having Formula (I) where the substituents R, R1-R5, k, m, n, and q are as defined herein. These compounds are used in the treatment of cancer, immunologic disorders, autoimmune disorders, neurodegenerative disorders, or inflammatory disorders, infectious disease, or for providing immunosuppression for transplanted organs or tissues.
Owner:CORNELL UNIVERSITY
Method for Inhibiting Cancer Using Arsenic Trioxide
It has been discovered that As2O3 suppresses tyrosine kinase receptors, in particular EGFR and IL-6R, by targeting RTKs to lysosomes and / or proteasome for degradation. This is the basis for the discovery that cancers dependent on RTKs for signaling, proliferation, survival, metastasis and differentiation can be treated with As2O3, preferably oral As2O3. Representative cancers include EGFR and cytokine dependent cancers, for example, head and neck squamous sarcomas and multiple myelomas, respectively.
Owner:THE UNIVERSITY OF HONG KONG
Nucleic acid encoding proteins involved in protein degradation, products and methods related thereof
Owner:BURNHAM INST FOR MEDICAL RES THE
Degradation of PA200 and acetylation-mediated core histones through proteasome
ActiveCN103191412APromote degradationIncreased sensitivityPeptide/protein ingredientsHydrolasesDNA repairTestis specific
The invention discloses an application of PA200 proteins in preparation of products. The products have at least one of the following functions from (1) to (4): (1) combining with acetylated proteins; (2) promoting the degradation of the acetylated proteins; (3) participating in repair of DNA (deoxyribonucleic acid) damages of somatic cells; and (4) participating in the formation of sperms. The invention has breakthroughs in four following aspects: (1) finding a mechanism of regulation and control of degradation of the histones, the sperm formation and the DNA repair by acetylation; (2) revealing the degradation of the histones medicated by acetylation rather than ubiquitination through PA200 / Blm10 proteasome; (3) finding novel testis-specific proteasome containing PA200 and alpha 4s, and revealing the core histones as a first type biological substrate for the proteasome; and (4) revealing that a histone deacetylase inhibitor can promote the degradation of the histones which are induced by DNA double-strand breaks and medicated by acetylation, enhance the sensitivity of cells to DNA damages and easily lead to the death of the cells.
Owner:BEIJING NORMAL UNIVERSITY
Methods for increasing learning and memory in amyloid-beta-related neurodegenerative disorders by increasing Uch-L1 activity and methods for identifying enhancers of Uch-L1 activity
InactiveUS20070071724A1Easy to learnEnhance memoryHydrolasesPeptide/protein ingredientsProteasome degradationAmyloid beta
The invention is directed to methods for increasing learning and memory in a subject with a neuropathological condition, specifically a condition related to elevated beta-amyloid deposition, the method comprising administering to the subject an effective amount of a compound capable of increasing the activity of Uch-L1. The invention is also directed to screening methods for identifying compounds that enhance the activity of the proteasome system, Uch-L1, or both.
Owner:THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
Methods and compositions for rapid purification of proteasomes and methods of use of components thereof
InactiveUS20060281118A1Fast wayHigh affinityHydrolasesMicroorganismsProteasome degradationUbiquitins
Disclosed are methods for rapidly and efficiently purifying proteasomes using fusion proteins having homology to ubiquitin. Also disclosed are methods for assessing aberrant cell growth utilizing fusion proteins have homology to ubiquitin and a signal producing moiety.
Owner:RUTGERS THE STATE UNIV
Methods for Inhibiting Proteasome and Heat Shock Protein 90
InactiveUS20070249540A1Improve anti-tumor effectDipeptide ingredientsAntipyreticProteasome degradationHeat shock protein
The present application provides methods for the inhibition of proteasome and heat shock protein Hsp90.
Owner:PAPATHANASSIU ADONIA
Proteasome inhibiting beta-lactam compounds
Owner:PRESIDENT & FELLOWS OF HARVARD COLLEGE
Methods For Producing Dendritic Cells That Have Acquired Ctl-Inducing Ability
InactiveUS20080194020A1Promotion of antigenic protein polyubiquitinationEnhance antigen presentationSugar derivativesPeptide preparation methodsProteasomeCross-presentation
The present inventors worked on elucidating the mechanism of antigen cross-presentation by dendritic cells, and revealed that foreign antigens taken up in dendritic cells are degraded by proteasomes after undergoing polyubiquitination. Based on the novel finding that polyubiquitination is involved in cross-presentation, the promotion of polyubiquitination was attempted by a number of methods, and the promotion of antigen presentation was confirmed. These methods enable the production of dendritic cells effective for inducing CTL activation.
Owner:KEIO UNIV +1
Controlling availability or activity of proteins by use of protease inhibitors or receptor fragments
InactiveUS20050250702A1Inhibiting proteolytic cleavage and truncationSignal transductionDipeptide ingredientsTripeptide ingredientsProteinase activityProteasome degradation
Owner:RECHARGE
Treatment of Hepatitis C Infection With Metalloporphyrins
InactiveUS20100086519A1Lower Level RequirementsReduction of NS5A protein levelBiocidePeptide/protein ingredientsInfected cellPost translational
The present invention is directed to the treatment of hepatitis C infection with a metalloporphyrin. In particular, the present invention is based on the discovery that the NS5A protein plays a key role in HCV RNA replication by participating in polyprotein cleavage, interferon response and cellular signaling pathways. It has been found that metalloporphyrins, such as zinc porphyrins, induce post-translational down-regulation of HCV NS5A protein in an ubquitin-proteasome degradation pathway. That is, metalloporphyrins can be used to activate the ubiquitin-proteasomal pathway of NS5A protein catabolism. As a result, metalloporphyrins can be used to significantly suppress HCV viral replication in HCV infected cells.
Owner:CHARLOTTE MECKLENBURG HOSPITAL AUTHORITY
Screening method of anti-HIV drug
InactiveCN101591645AAddressing drug resistanceNo cross resistanceMicrobiological testing/measurementVector-based foreign material introductionScreening methodCross-resistance
The invention discloses a screening method of an anti-HIV drug, which comprises the following steps: a sample to be tested is added to a fusion protein which expresses hA3G and reporter gene and a Vif cell; the blocking effect of the sample on Vif pathway is judged by investigating the quantity of the encoding products of the reporter gene; whether the initially chosen sample is an inhibitor in the pathway of proteasome degradation is further judged to screen out the anti-HIV drug. In the method provided by the invention, a hA3G is taken as a target point, solves the problem of drug resistance caused by high mutation of viruses and has no cross resistance with the anti-HIV-1 drug used in clinical application for the moment.
Owner:MEDICINE & BIOENG INST OF CHINESE ACAD OF MEDICAL SCI
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