Design, Synthesis, and Biological Evaluation of Proteolysis Targeting Chimeras (PROTACs) for the Dual Degradation of IGF-1R and Src.

ABSTRACT: A focused PROTAC library was developed to degrade both IGF-1R and Src proteins, which are associated with various cancers. PROTACs with IGF-1R and Src degradation potentials were synthesized by tethering different inhibitor warhead units and the E3 ligase (CRBN) recruiting-pomalidomide with various linkers. The designed PROTACs 12a-b inhibited the proliferation and migration of MCF7 and A549 cancer cells with low micromolar potency (1-5 μM) in various cellular assays.

SUBMITTER: Manda S 

PROVIDER: S-EPMC7221895 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature