Design and synthetic approaches to thalidomide based small molecule degraders.

Thalidomide has been used as a repurposed drug for treating multiple myeloma since 1997. Several novel anticancer drugs containing thalidomide active moiety has been discovered since then. Many thalidomide drug candidates with tuned linker size have been instrumental in inhibiting histone deacetylase, kinase, transcription factors etc. and facilitate selective degradation of E3 ligase and other enzymes. Here we are focused on small molecule degraders that are being tailored with tweaking synthetic architectures around thalidomide chemical motif towards the development of promising drug candidates. Interesting biomedical applications of thalidomide-based degraders with recent developments including pharmacokinetic profiles, protein stability, activity studies, degradation assays, and antitumor response are elucidated.