160 results about "Cereblon" patented technology

This invention provides Degrons and Degraders that covalently bind to cereblon which is a component of the E3 ubiquitin ligase. The Degrons provided herein can be used to modulate the activity of cereblon either alone or as covalently linked to a Tail. In addition, the Degron can be linked to a Targeting Ligand which binds to a Target Protein to provide a Degrader.

Bifunctional compounds, which find utility as modulators of leucine-rich repeat kinase 2 (LRRK2), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds LRRK2, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation / inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

Bifunctional compounds, which find utility as modulators of B-cell lymphoma 6 protein (BCL6; target protein), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a Von Hippel-Lindau, cereblon, Inhibitors of Apotosis Proteins or mouse double-minute homolog 2 ligand that 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 bifunctional compounds of the present disclosure exhibit 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 present disclosure relates to bifunctional compounds, which find utility to degrade (and inhibit) Androgen Receptor. In particular, the present disclosure is directed to compounds, which contain on one end a cereblon ligand which binds to the E3 ubiquitin ligase and on the other end a moiety which binds Androgen Receptor, such that Androgen Receptor is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of Androgen Receptor. The present disclosure exhibits a broad range of pharmacological activities associated with compounds according to the present disclosure, consistent with the degradation / inhibition of Androgen Receptor.

This invention provides Degronimers that have E3 Ubiquitin Ligase targeting moieties (Degrons) that can be linked to a targeting ligand for a protein that has been selected for in vivo degradation, and methods of use and compositions thereof as well as methods for their preparation. The invention also provides Degrons that can be used to treat disorders mediated by cereblon or an Ikaros family protein, and methods of use and compositions thereof as well as methods for their preparation.

Provided herein are cerebron degrading agent antibody conjugates (cDACs) comprising a cerebron degrading agent moiety covalently linked to an antibody. The cDACs target proteins for intracellular degradation and can be used to treat diseases and conditions.

This text describes bifunctional compounds that can be used as modulators of non-receptor leucine-rich repeat kinase 2 (LRRK2). In particular, the bifunctional compounds of the present disclosure contain a moiety that binds to the cereblon E3 ubiquitin ligase at one end and a moiety that binds to LRRK2 at the other end, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of the target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities related to degradation / inhibition of the target protein. Treat or prevent diseases or disorders caused by abnormal regulation of the target protein with the compounds and compositions of the present disclosure.

The present invention provides compounds, pharmaceutically acceptable compositions thereof, and methods of using the same for the modulation of one or more SWI / SNF-related matrix associated actin dependent regulator of chromatin subfamily A (SMARCA) and / or polybromo-1 (PB-1) protein via ubiquitination and / or degradation by compounds. The compounds are bifunctional molecules that link a cereblon-binding moiety to a ligand that binds SMARCA and / or PB1 proteins.

Bifunctional compounds, which find utility as modulators of Rapidly Accelerated Fibrosarcoma (Raf, such as c-Raf, A-Raf, and / or B-Raf), are described herein. In particular, the hetero-bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds Raf, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The hetero-bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation / inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

This document provides bifunctional compounds, one part of which (e.g., lenalidomide, thalidomide) is a binder of an E3 ubiquitin ligase (e.g., Cereblon) and the other part of which is a binder of a target protein (e.g., a kinase (e.g., CDK (e.g., CDK9 and / or CDK12))) to induce the degradation of the target protein CDK9 and / or CDK12. Pharmaceutical compositions comprising bifunctional compounds are also provided, as well as methods for treating and / or preventing diseases (e.g., proliferative diseases such as cancers (e.g., ovarian cancer, breast cancer, or prostate cancer)). Methods for inducing the degradation of target proteins (e.g., kinases (e.g., CDK (e.g., CDK9 and / or CDK12))) and methods for inducing apoptosis in biological samples or subjects by administering the bifunctional compounds or compositions described herein are also provided.

Certain Androgen receptor PROTAC (PROteolysis TArgeting Chimera) compounds contain a series of 2,4-dioxotetrahydropyrimidinyl derivatives that bind cereblon. The PROTAC compounds may be viewed as being comprised of an androgen receptor binding moieties, a linker and a cereblon binding moiety or degron. Medical uses of these PROTAC compounds are also disclosed.

Compounds and pharmaceutical compositions useful to treat cancer (e.g., lymphoma), neurodegenerative diseases, and autoimmune disorders include (1) a first nucleic acid sequence capable of binding to a transcription factor, for example, a signal transducer and activator of transcription (STAT) factor, such as STAT3, (2) a second nucleic acid sequence capable of binding a Toll-like receptor protein, for example, a CpG oligodeoxynucleotide, and (3) a ubiquitin ligase binding compound capable of binding a ubiquitin ligase protein, for example, a compound that is capable of binding a cereblon protein, such as lenalidomide, pomalidomide, or thalidomide.

The present disclosure relates to novel compounds that act as modulators of cereblon (CRBN). The compounds promote CRBN-mediated ubiquitination and proteasomal degradation of oncogenic proteins such as GSPT1 and MYC, thereby suppressing abnormal cell growth. Pharmaceutical compositions containing the compounds and methods of using the compositions for the treatment of cancers, particularly solid tumors, are also provided.

The present application discloses compounds of Formula (I) that modulate splicing of a pre-mRNA, encoded by genes, and methods of treating diseases and conditions associated with gene expression or activity of proteins encoded by genes, such as Spinocerebellar Ataxia 3 (SCA3 or Machado-Joseph Disease).

The present disclosure relates to salts and solid forms of compounds that bind to cereblon, thereby modulating cereblon activity and methods of using the same in the treatment of various IKZF2-mediated diseases or disorders, such as proliferative diseases or disorders and / or cancer.

The present disclosure relates to a compound of Formula (I) or a salt, enantiomer, diastereomer, isotopically enriched analogue, solvate, prodrug or polymorph thereof, and the use thereof. Further provided in the present disclosure are a pharmaceutical composition comprising, as an active ingredient, the compound of Formula (I) or a salt, enantiomer, diastereomer, isotopically enriched analogue, solvate, prodrug or polymorph thereof, and the use thereof. A series of compounds designed and synthesized in the present disclosure can effectively prevent and / or treat diseases or disorders associated with cereblon protein.

This text describes bifunctional compounds that can be used as regulators of leucine-rich repeat kinase 2 (LRRK2). In particular, the heterobifunctional compounds of the present disclosure contain a moiety that binds to the cereblon E3 ubiquitin ligase at one end and a moiety that binds to LRRK2 at the other end, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of the target protein. The heterobifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities related to the degradation / inhibition of the target protein. Treat or prevent diseases or disorders caused by abnormal regulation of the target protein with the compounds and compositions of the present disclosure.

The present invention relates to a use of a novel pomalidomide derivative which is for treating brain diseases, and exhibits improved pharmacological effects as compared to pomalidomide. The novel pomalidomide derivative according to the present invention exhibits excellent binding to cereblon, has almost no cytotoxicity, is unlikely to cause teratogenic adverse effects, can control TNF-α expression, exhibits excellent in vivo pharmacokinetic stability while suppressing oxidative stress, ameliorates a decrease in motor function which is a symptom of Parkinson's disease, and increases tyrosine hydroxylase expression which is reduced by Parkinson's disease, and thus can be used for preventing or treating brain diseases such as Parkinson's disease.

The present invention addresses the problem of providing a novel compound having a Cerebron E3 ligase binding ability. It is possible to provide a compound represented by formula (I) [in the formula, each symbol is as set forth in the description], formula (II) [in the formula, each symbol is as set forth in the description], formula (III) [in the formula, each symbol is as set forth in the description], or formula (IV) [in the formula, each symbol is as set forth in the description], or a pharmacologically acceptable salt thereof. # imgabs0 #

The present invention relates to a compound represented by formula (I), or an isomer, isotope derivative, polymorph, prodrug thereof, or a pharmaceutically acceptable salt or solvate thereof: wherein R1, R2, R3a, R3b, R3c, R3d, W1, W2, G, Z and n are as described. The compound of formula I is a human cereblon (CRBN) E3 ubiquitin ligase inhibitor, which can be used for preparing PROTAC molecules. The CRBN E3 ubiquitin ligase inhibitor and PROTAC molecule can be used to treat cancer and other diseases.

A compound of formula I or a stereoisomer, isotopic isomer, tautomer or pharmaceutically acceptable salt thereof: wherein a ligand that binds to Nef protein (NB) is covalently linked to a ligand that binds to E3 ligase cerebron (CB) via a linker (L).

Provided herein are targeting constructs for sustained transgene expression of inducible cell death systems that include degron mutants and cereblon mutants. Also provided are pharmaceutical compositions comprising the targeting constructs, and methods for use of the same. The methods of use include methods of inducing cell death in a cell, and methods of treating patients in need thereof.

This invention provides heterocyclic compounds that bind to E3 Ubiquitin Ligase (typically through cereblon) (“Degrons”), which can be used as is or linked to a Targeting Ligand for a selected Target Protein for therapeutic purposes and methods of use and compositions thereof as well as methods for their preparation.

Disclosed are compounds and salts thereof that bind to and modulate the activity of cereblon. In some embodiments, the binding and modulation of cereblon results in the degradation of IKAROS family zinc finger proteins (e.g., IKZF2). The compounds are represented by Formula I: TIFF2026502995000081.tif43170

Bifunctional compounds, which find utility as modulators of androgen receptor (AR), are described herein. In particular, the bifunctional compounds of the present disclosure contain on one end a moiety that binds to the cereblon E3 ubiquitin ligase and on the other end a moiety which binds AR, such that the target protein is placed in proximity to the ubiquitin ligase to effect degradation (and inhibition) of target protein. The bifunctional compounds of the present disclosure exhibit a broad range of pharmacological activities associated with degradation / inhibition of target protein. Diseases or disorders that result from aberrant regulation of the target protein are treated or prevented with compounds and compositions of the present disclosure.

A pomalidomide derivative exhibiting effects better than those of pomalidomide, a preparation method therefor, and use thereof. The pomalidomide derivative has excellent binding force to cereblon, has low cytotoxicity, has a low potential for causing teratogenic side effects, can regulate the expression of TNF-α and proinflammatory cytokines, and has excellent in vivo pharmacokinetic stability even while inhibiting oxidative stress.

To provide compounds that find utility as modulators of RapidlyAcceleratedFibrosarcoma (RAF, such as c-RAF, A-RAF and / or B-RAF; target proteins).SOLUTION: The present invention is directed to bifunctional compounds that contain a von Hippel-Lindau, cereblon, Inhibitorsof Apoptosis Proteins, or mousedouble-RAF ligand that binds to the respective E3 ubiquitin ligase at one end and a moiety that binds to the target proteins RAF at the other end, such that the target proteins are placed in proximity to the ubiquitin ligase to effect degradation (and minutehomolog2) of the target proteins. The present disclosure presents a wide range of pharmacological activities related to degradation / inhibition of target proteins.SELECTED DRAWING: None

To provide compounds useful as modulators of targeted ubiquitination, and as inhibitors with respect to a variety of polypeptides and other proteins.SOLUTION: A specific compound has the chemical structure comprising: L-CLM, wherein: L is a linker group; CLM is a cereblon E3 ubiquitin ligase binding moiety; and the linker group is chemically linked to the CLM. Pharmaceutically acceptable salts, enantiomers, stereoisomers, solvates or polymorphs are also provided.SELECTED DRAWING: Figure 1

Disclosed are small molecules against cereblon to enhance effector T cell function. Methodos of making thes molecules and methods of using them to treat various disease states are also disclosed.

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 a cereblon, Von Hippel-Lindau ligase-binding moiety, Inhibitors of Apotosis Proteins, or mouse double-minute homolog 2 ligand, 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.