An active metabolite of thalidomide and a PROTAC synthetic intermediate
E3 ligase ligand 2 is an active metabolite of thalidomide and an intermediate in the synthesis of proteolysis-targeting chimeras (PROTACs) containing thalidomide, a ligand for the E3 ubiquitin ligase cereblon (CRBN), used in targeted protein degradation.1,2 E3 ligase ligand 2 is formed from thalidomide via hydroxylation. It decreases the production of TNF-α induced by 12-O-tetradecanoylphorbol 13-acetate in THP-1 cells when used at a concentration of 30 ?M.3 E3 ligase ligand 2 (333 ?M) completely inhibits the proliferation of human umbilical vein endothelial cells (HUVECs). It inhibits VEGF- and FGF2-induced angiogenesis by 14% in a chicken chorioallantoic membrane (CAM) assay in utero when administered at a dose of 100 ?g/embryo.1
1.Marks, M.G., Shi, J., Fry, M.O., et al.Effects of putative hydroxylated thalidomide metabolites on blood vessel density in the chorioallantoic membrane (CAM) assay and on tumor and endothelial cell proliferationBiol. Pharm. Bull.25(5)597-604(2002) 2.Robb, C.M., Contreras, J.I., Kour, S., et al.Chemically induced degradation of CDK9 by a proteolysis targeting chimera (PROTAC)Chem. Commun. (Camb.)53(54)7577-7580(2017) 3.Nakamura, T., Noguchi, T., Kobayashi, H., et al.Mono- and dihydroxylated metabolites of thalidomide: Synthesis and TNF-α production-inhibitory activityChem. Pharm. Bull. (Tokyo)54(12)1709-1714(2006)
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