136 results about "Cereblon" patented technology

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.

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.

Aβ_N3pE-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 Aβ_N3pE-42 and can be expected to have a strong β amyloid-removing action. Particularly, humanized antibodies against Aβ_N3pE-42 are useful to treat human neurodegenerative diseases. Further, since Aβ_N3pE-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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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.

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.

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.