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 (0-1 μM; 72 hours) decreases cell growth with an EC 50 value of 21.3 nM, which is comparable to the cellular potency of sunitinib (EC 50 =17.3 nM)[1].MI-389 (0-500 nM; 72 hours) leads to GSPT1 destabilization fastly as a dosepdependent manner. It shows a complete GSPT1 depletion at 100 nM[1]. Cell Viability Assay[1]Cell Line: Kasumi-1 cells (a c-KIT dependent acute myeloid leukemia (AML) cell line); GIST-T1 Concentration: 0-1 μM Incubation Time: 72 hours Result: Outperform decreased-antiproliferative effect than sunitinib Western Blot Analysis[1]Cell Line: Kasumi-1 cells (a c-KIT dependent acute myeloid leukemia (AML) cell line); GIST-T1 Concentration: 1 nM, 5 nM, 10 nM, 50 nM, 100 nM, 500 nM Incubation Time: 4 hours Result: Decreased GSPT-1 protein expression.