COMPOUNDS AND METHODS FOR THE ENHANCED DEGRADATION OF TARGETED PROTEINS AND OTHER POLYPEPTIDES BY AN E3 UBIQUITIN LIGASE

• Main Authors: Miah, Afjal Hussain, Hoyer, Dentin Wade, Michel, Julien, Crews, Craig M, Tae, Hyun-Seop, Molle, Inge Van, Buckley, Dennis, Roth, Anke G, Gustafson, Jeffrey, Le, Joelle, Smith, Ian Edward David, Ciulli, Alessio, Gareiss, Peter C, Harling, John David, Campos, Sebastien Andre, Jorgensen, William
• Format: Patent
• Language: English
• Published: 11.04.2024
• Subjects: BEER; BIOCHEMISTRY; CHEMISTRY; COMPOSITIONS OR TEST PAPERS THEREFOR; CONDITION-RESPONSIVE CONTROL IN MICROBIOLOGICAL ORENZYMOLOGICAL PROCESSES; ENZYMOLOGY; HETEROCYCLIC COMPOUNDS; MEASURING OR TESTING PROCESSES INVOLVING ENZYMES, NUCLEICACIDS OR MICROORGANISMS; METALLURGY; MICROBIOLOGY; MUTATION OR GENETIC ENGINEERING; ORGANIC CHEMISTRY; PEPTIDES; PROCESSES OF PREPARING SUCH COMPOSITIONS; SPIRITS; STEROIDS; VINEGAR; WINE

The present invention relates to bifunctional compounds, 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 present invention is directed to compounds, which contain on one end a VHL ligand which binds to the 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. The present invention exhibits a broad range of pharmacological activities associated with compounds according to the present invention, consistent with the degradation/inhibition of targeted polypeptides.