- IRAK DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 00962; 001770; 001773-001774; 001798-001799
(2020/06/19)
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- DIMERIC IMMUNO-MODULATORY COMPOUNDS AGAINST CEREBLON-BASED MECHANISMS
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Disclosed are small molecules against cereblon to enhance effector T cell function. Methods of making these molecules and methods of using them to treat various disease states are also disclosed.
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Page/Page column 96; 100
(2020/02/06)
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- STAT DEGRADERS AND USES THEREOF
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The present invention provides compounds, compositions thereof, and methods of using the same.
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Paragraph 0001030; 0001031
(2020/10/19)
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- BRM TARGETING COMPOUNDS AND ASSOCIATED METHODS OF USE
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The present disclosure relates to bifunctional compounds, which find utility as modulators of SMARCA2 or BRM (target protein). In particular, the present disclosure is directed to bifunctional compounds, which contain on one end a ligand that binds to the Von Hippel-Lindau 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.
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- A "click Chemistry Platform" for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation
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Proteolysis targeting chimeras (PROTACs) are bispecific molecules containing a target protein binder and an ubiquitin ligase binder connected by a linker. By recruiting an ubiquitin ligase to a target protein, PROTACs promote ubiquitination and proteasomal degradation of the target protein. The generation of effective PROTACs depends on the nature of the protein/ligase ligand pair, linkage site, linker length, and linker composition, all of which have been difficult to address in a systematic way. Herein, we describe a "click chemistry" approach for the synthesis of PROTACs. We demonstrate the utility of this approach with the bromodomain and extraterminal domain-4 (BRD4) ligand JQ-1 (3) and ligase binders targeting cereblon (CRBN) and Von Hippel-Lindau (VHL) proteins. An AlphaScreen proximity assay was used to determine the ability of PROTACs to form the ternary ligase-PROTAC-target protein complex and a MSD assay to measure cellular degradation of the target protein promoted by PROTACs.
- Wurz, Ryan P.,Dellamaggiore, Ken,Dou, Hannah,Javier, Noelle,Lo, Mei-Chu,McCarter, John D.,Mohl, Dane,Sastri, Christine,Lipford, J. Russell,Cee, Victor J.
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p. 453 - 461
(2018/02/07)
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- An iterative route to "decorated" ethylene glycol-based linkers
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Iterative copper-catalyzed cycloadditions of azides to alkynes were used to join functionalized triethylene glycol molecules to give "linkers" of defined lengths equipped with several different end-group functionalities. The Royal Society of Chemistry 200
- Lu, Genliang,Lam, Sang,Burgess, Kevin
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p. 1652 - 1654
(2008/02/08)
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