Thalidomide-NH-C6-NH-Boc is a synthesized E3 ligase ligand-linker conjugate containing the cereblon ligand derived from Thalidomide and a linker utilized in the synthesis of MI-389 (compound 22). MI-389 is a highly effective phthalimide PROTAC degrader developed from the multi-targeted receptor tyrosine kinase inhibitor sunitinib.

MI-389, at concentrations ranging from 0-1 μM over 72 hours, significantly reduces cell growth with an EC50 of 21.3 nM, showcasing a potency similar to that of sunitinib, which has an EC50 of 17.3 nM[1]. Additionally, MI-389 induces rapid dose-dependent GSPT1 destabilization across a 0-500 nM range, achieving complete depletion at 100 nM[1]. In Kasumi-1 cells, a c-KIT dependent acute myeloid leukemia (AML) cell line, and GIST-T1 cells, MI-389 demonstrates a superior antiproliferative effect compared to sunitinib when tested at 0-1 μM for 72 hours[1]. Western blot analysis reveals that MI-389 decreases GSPT-1 protein expression in a dose-dependent manner within 4 hours across incremental concentrations from 1 nM to 500 nM[1].