888010-02-4Relevant articles and documents
IRAK DEGRADERS AND USES THEREOF
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Paragraph 00962; 001770; 001773-001774; 001798-001799, (2020/06/19)
The present invention provides compounds, compositions thereof, and methods of using the same.
STAT DEGRADERS AND USES THEREOF
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Paragraph 0001030; 0001031, (2020/10/19)
The present invention provides compounds, compositions thereof, and methods of using the same.
A "click Chemistry Platform" for the Rapid Synthesis of Bispecific Molecules for Inducing Protein Degradation
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.
, p. 453 - 461 (2018/02/07)
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.
