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From Thalidomide to Rational Molecular Glue Design for Targeted Protein Degradation
Annu Rev Pharmacol Toxicol. 2023 Aug 16. doi: 10.1146/annurev-pharmtox-022123-104147. Online ahead of print.ABSTRACTThalidomide and its derivatives are powerful cancer therapeutics that are among the best-understood molecular glue degraders (MGDs). These drugs selectively reprogram the E3 ubiquitin ligase cereblon (CRBN) to commit target proteins for degradation by the ubiquitin-proteasome system. MGDs create novel recognition interfaces on the surface of the E3 ligase that engage in induced protein-protein interactions with neosubstrates. Molecular insight into their mechanism of action opens exciting opportunities to eng...
Source: Annual Review of Pharmacology and Toxicology - August 16, 2023 Category: Drugs & Pharmacology Authors: Vladas Oleinikovas Pablo Gainza Thomas Ryckmans Bernhard Fasching Nicolas H Thom รค Source Type: research
