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138 results about "Cereblon" patented technology

Cereblon is a protein that in humans is encoded by the CRBN gene. The gene that encodes the cereblon protein is found on the human chromosome 3, on the short arm at position p26.3 from base pair 3,190,676 to base pair 3,221,394. CRBN orthologs are highly conserved from plants to humans.

Imide-based modulators of proteolysis and associated methods of use

InactiveUS20160058872A1Organic active ingredientsCompound screeningCereblonProteolytic Regulation
The description relates to imide-based compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and / or otherwise inhibited by bifunctional compounds according to the present invention. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation / inhibition of targeted polypeptides of nearly any type.
Owner:ARVINAS OPERATIONS INC

Conjugates of cereblon binding compounds and g12c mutant kras, hras or nras protein modulating compounds and methods of use thereof

ActiveUS20180015087A1Inhibiting KRAS-G12C oncogenic activityDecreasing KRAS-G12C protein levelOrganic active ingredientsPharmaceutical non-active ingredientsCereblonDisease
Conjugates of a cereblon-binding compound and compounds having modulatory activity against G12C mutant KRAS, HRAS or NRAS G12C proteins are provided. Methods associated with preparation and use of such conjugates, pharmaceutical compositions comprising such conjugates and methods to modulate the activity of G12C mutant KRAS, HRAS or NRAS G12C proteins for treatment of disorders, such as cancer, are also provided.
Owner:ARAXES PHARMA LLC

Amyloid beta-protein 3(pE)-42 antibodies and uses thereof

AβN3pE-42 is a β amyloid protein that accumulates specifically as a major constituent of senile plaque in the brains of both sporadic and familial Alzheimer's disease patients. The invention provides antibodies that specifically recognize AβN3pE-42 and can be expected to have a strong β amyloid-removing action. Particularly, humanized antibodies against AβN3pE-42 are useful to treat human neurodegenerative diseases. Further, since AβN3pE-42 is localized in the brain, the antibodies of the invention can avoid side effects such as kidney disorders caused by the formation of antigen-antibody complex in the blood. An agent for gene therapy using a vector in which a cDNA encoding a protein comprises the antigen-binding region of the antibody can be an efficient therapeutic drug for removing β amyloid from the brain.
Owner:SAIDO TAKAOMI +1

Cereblon ligands and bifunctional compounds comprising the same

The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and / or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation / inhibition of targeted polypeptides of nearly any type.
Owner:ARVINAS OPERATIONS INC

Cereblon ligands and bifunctional compounds comprising the same

The description relates to cereblon E3 ligase binding compounds, including bifunctional compounds comprising the same, which find utility as modulators of targeted ubiquitination, especially inhibitors of a variety of polypeptides and other proteins which are degraded and / or otherwise inhibited by bifunctional compounds according to the present disclosure. In particular, the description provides compounds, which contain on one end a ligand which binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds a target protein such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of that protein. Compounds can be synthesized that exhibit a broad range of pharmacological activities consistent with the degradation / inhibition of targeted polypeptides of nearly any type.
Owner:ARVINAS OPERATIONS INC

Methods for determining drug efficacy using cereblon-associated proteins

Use of cereblon-associated proteins as biomarkers for clinical sensitivity to cancer, inflammatory diseases, and patient response to drug treatment.
Owner:CELGENE CORP

Methods for determining drug efficacy for the treatment of diffuse large b-cell lymphoma, multiple myeloma, and myeloid cancers

Provided herein, in some embodiments, are methods of using certain cereblon-associated proteins, such as Aiolos, Ikaros, interferon (IFN), and IFN pathway proteins, casein kinase 1, alpha 1 (CSNK1A1), and ZFP9, as biomarkers for use in predicting and monitoring clinical sensitivity and therapeutic response to certain compounds in patients having various diseases and disorders, such as cancers (e.g., diffuse large B-cell lymphoma (DLBCL), multiple myeloma (MM), myelodysplasia syndromes (MDS) and acute myeloid leukemia (AML)) and IFN-associated disorders. Also provided herein, in certain embodiments, are methods of determining the efficacy of an immunomodulatory compound.
Owner:CELGENE CORP

Upregulating bdnf levels to mitigate mental retardation

This invention provides methods of preserving, improving, or restoring cognitive function in mammal having one or more mutations in the FMR1 gene (e.g. at risk for or having fragile x syndrome), where the methods involve the brain derived neurotrophic factor (BDNF) level or activity in the brain of said mammal. In certain embodiments the methods involve administering one or more AMPA potentiators (e.g., ampakines) to the mammal in an amount sufficient to increase BDNF levels in the brain of the mammal.
Owner:RGT UNIV OF CALIFORNIA

Methods to induce targeted protein degradation through bifunctional molecules

The present application provides bifunctional compounds which act as protein degradation inducing moieties. The present application also relates to methods for the targeted degradation of endogenous proteins through the use of the bifunctional compounds that link a cereblon-binding moiety to a ligand that is capable of binding to the targeted protein which can be utilized in the treatment of proliferative disorders. The present application also provides methods for making compounds of the application and intermediates thereof.
Owner:DANA FARBER CANCER INST INC

Immunogenic peptide composition comprising measles virus Fprotein Thelper cell epitope (MUFThl-16) and N-terminus of β-amyloid peptide

The present invention relates to a composition comprsing a peptide immunogen useful for the prevention and treatment of Alzheimer's Disease. More particularly, the peptide immunogen comprises a main functional / regulatory site, an N-terminal fragment of Amyloid β (Aβ) peptide linked to a helper T cell epitope (Th) having multiple class II MHC binding motifs. The peptide immunogen elicit a site-directed immune response against the main functional / regulatory site of the Aβ peptide and generate antibodies, which are highly cross-reactive to the soluble Aβ1-42 peptide and the amyloid plaques formed in the brain of Alzheimer's Disease patients. The antibodies elicited being cross reactive to the soluble Aβ1-42 peptide, promote fibril disaggregation and inhibit fibrillar aggregation leading to immunoneutralization of the “soluble Aβ-derived toxins”; and being cross-reactive to the amyloid plaques, accelerate the clearance of these plaques from the brain. Thus, the composition of the invention comprising the peptide immunogen is useful for the prevention and treatment of Alzheimer's Disease.
Owner:UNITED NEUROSCIENCE LIMITED

Non-invasive vagal nerve stimulation to treat disorders

ActiveUS20150032178A1Generate lotReduced level of neurotransmitter levelElectrotherapyMagnetotherapy using coils/electromagnetsDiseaseNon invasive
Devices, systems and methods are disclosed for treating a variety of diseases and disorders that are primarily or at least partially driven by an imbalance in neurotransmitters in the brain, such as asthma, COPD, depression, anxiety, epilepsy, fibromyalgia, and the like. The technology involves the use of an energy source comprising magnetic and / or electrical energy that is transmitted non-invasively to, or in close proximity to, a selected nerve to temporarily stimulate, block and / or modulate the signals in the selected nerve such that neural pathways are activated to release inhibitory neurotransmitters in the patient's brain.
Owner:ELECTROCORE

Rabies cure

This invention is for a method of treatment of rabies once the patient develops signs and symptoms of rabies with the intent to save the patients from death and disability using insulin combined with various anti rabies viral therapeutic, pharmaceutical, biochemical, and biological agents or compounds with added supportive therapies administered through OM, SAS, IVB, IV, and IA routes. An embodiment provides devices for intranasal delivery of therapeutic agents to olfactory mucosal area. Another embodiment uses the technology to deliver the therapeutic, pharmaceutical, biochemical, and biological agents or compounds to the subarachnoid space and ventricular system by using continuous catheters and Ommaya reservoir at the same time. The present method incorporates breaking the blood brain barrier to allow the entry of the anti rabies therapeutic agents into the neuropile. Additionally, an embodiment incorporates cooling of the brain and inducing hibernation to preserve the brain from damage due to rabies.
Owner:SHANTHA TOTADA R

Antisense oligonucleotides tarageting folate receptor alpha, and the use thereof

The invention relates to treatment of cancers and cancerous cells which over-express α folate receptor (FRα) compared to the normal cells of the same tissue. The invention is directed to antisense oligonucleotides which are complimentary to the coding region of FRα, as well as the pharmaceutical compositions made thereof, and the methods of using the same for treatment of cancers, e.g. cancers of ovary, cervix, uterus, and brain.
Owner:FOLIGO THERAPEUTICS

Tau-protein targeting protacs and associated methods of use

The present disclosure relates to bifunctional compounds, which find utility as modulators of tau protein. In particular, the present disclosure is directed to bifunctional compounds, which contain onone end a VHL or cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds tau protein, such that tau protein is placed in proximity to the ubiquitin ligase toeffect degradation (and inhibition) of tau. The present disclosure exhibits a broad range of pharmacological activities associated with degradation / inhibition of tau protein. Diseases or disorders that result from aggregation or accumulation of tau protein are treated or prevented with compounds and compositions of the present disclosure.
Owner:ARVINAS

Metastasis Promoting Genes and Proteins

Two sets of genes and their encoded proteins, one set of 17 genes / proteins and one set of 18 genes / proteins that can be used in predicting the risk of cancer metastasis to the brain, and as a screening assay to identify the suitable treatments for brain metastases. Genes / proteins within the sets that are found to be differentially expressed relative to a control value are suitable targets for therapy.
Owner:SLOAN KETTERING INST FOR CANCER RES

Cereblon ligand-induced BET degradation-based bifunctional molecule and preparation and application thereof

The invention relates to a novel preparation method of a bifunctional molecule and a pharmaceutically acceptable salt, hydrate or prodrug thereof and application of these compounds and a medicinal composition thereof in treatment of diseases such as tumors, inflammation and immunity. The bifunctional molecule is a protein degradation-targeted complex (PROTACs), and is capable of selectively inducing BET protein degradation. A BET protein small-molecule inhibitor is connected with a cereblon protein ligand in an E3 ubiquitin ligase complex to obtain the bifunctional molecule.
Owner:CHINA PHARM UNIV

Tetrahydronaphthalene and tetrahydroisoquinoline derivatives as estrogen receptor degraders

The present disclosure relates to bifunctional compounds, which find utility as modulators of estrogen receptor (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end at least one of a Von Hippel-Lindau ligand, a cereblon ligand, Inhibitors of Apoptosis Proteins ligand, mouse double-minute homolog 2 ligand, or a combination thereof, which binds to the respective E3 ubiquitin ligase, and on the other end a moiety which binds the target protein, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The present disclosure exhibits a broad range of pharmacological activities associated with degradation / inhibition of target protein. Diseases or disorders that result from aggregation or accumulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.
Owner:ARVINAS OPERATIONS INC

Cereblon ligand mediated novel BET protein degradation bifunctional molecules, preparation and application thereof

The invention relates to a preparation method of new bifunctional small molecules and pharmaceutically acceptable salts, hydrates or prodrugs thereof, and application of the compounds and pharmaceutical compositions thereof in treatment of tumors, inflammation, immunity and other diseases. The bifunctional small molecules involved in the invention are protein degradation targeting chimeras (PROTACs), and can selectively induce BET protein degradation. According to the invention, a connecting arm is employed to connect a BET protein small molecule inhibitor and a cereblon protein ligand in theE3 ubiquitin ligase complex so as to obtain the bifunctional small molecules.
Owner:CHINA PHARM UNIV

Pyrrolopyridone double-functional molecule compound based on Cereblon ligand induced BET degradation

ActiveCN110204543AOrganic active ingredientsOrganic chemistryDiseaseUbiquitin ligase complex
The invention relates to a novel pyrrolopyridone double-functional molecule, and pharmaceutically acceptable salts, hydrates, prodrug thereof, and a pharmaceutical composition taking the novel pyrrolopyridone double-functional molecule as an active component, and applications of the above compounds and the pharmaceutical composition in treatment or prevention of tumor, inflammation, and immunity diseases. The double-functional molecule is a proteolytic targeting chimera (PROTAC); the preparation method is mature; connecting arms are adopted to connect BET protein small molecular inhibitors andCereblon protein ligand in E3 ubiquitin ligase complex so as to obtain the double-functional molecule; the obtained compound is capable of realizing selective induction of BET protein degradation; and the tumor prevention effect is obvious.
Owner:JIANGSU PROVINCE INST OF TRADITIONAL CHINESE MEDICINE +1

Preventing and treating amyloid-beta deposition by stimulation of innate immunity

ActiveUS20110060035A1Preventing and reducing amyloid depositionReducing amyloid depositionOrganic active ingredientsNervous disorderCereblonInnate immune system
The present invention is directed to a method of preventing or reducing amyloid deposition in a subject. This method involves selecting a subject with amyloid deposits and stimulating the innate immune system of the selected subject under conditions effective to reduce the amyloid deposits. Also disclosed is a method of preventing or treating cerebral amyloidosis and Alzheimer's Disease in a subject by administering to the selected subject an agent that stimulates the innate immune system. In addition, a composition useful for the stimulation of the innate immune system of a subject exhibiting symptoms associated with amyloid deposition is disclosed.
Owner:NEW YORK UNIV

Methods for determining drug efficacy for treatment of cancer using ratios of cereblon associated proteins

A method of identifying a subject having cancer who is likely to be responsive to a treatment compound, comprising administering a treatment compound to a subject having cancer; obtaining a sample from the subject; determining the ratio of a first biomarker level to a second biomarker level in the sample from the subject, wherein at least one of the biomarkers is a CRBN-associated protein; and diagnosing the subject as being likely to be responsive to the treatment compound if the ratio of the biomarker levels in the sample of the subject changes as compared to a reference ratio of the biomarker levels.
Owner:CELGENE CORP

Methods to treat alzheimer's disease using apoe inhibitors

InactiveUS20150337030A1Avoid defectsTreating and preventing and delaying onsetNervous disorderPolymorphism usesAntibody inhibitorLate onset
Non-familial late-onset Alzheimer's disease (LOAD), a condition associated with the accumulation of the amyloid precursor protein-derived (APP) Abeta fragment in the brain, can be the consequence of combined genetic and environmental risk factors. One of these risk factors is the presence of the apolipoprotein E4 (APOE4) allele. This invention provides for a neuron model that can be used to screen and identify compounds that can prevent the APOE4-induced pre-LOAD state. This invention provides for methods for the treatment and / or prevention of a neurodegenerative disorder by using an inhibitor of APOE4, such as an antibody inhibitor, or by using an excess of APOE3 protein.
Owner:THE TRUSTEES OF COLUMBIA UNIV IN THE CITY OF NEW YORK
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