Novel immunomodulatory drugs and neo-substrates

摘要: Thalidomide, lenalidomide and pomalidomide are immunomodulatory drugs (IMiDs) effective in the treatment of multiple myeloma, myelodysplastic syndrome (MDS) with deletion chromosome 5q other hematological malignancies. Recent studies showed that IMiDs bind to CRBN, a substrate receptor CRL4 E3 ligase, induce ubiquitination degradation IKZF1 IKZF3 myeloma cells, contributing their anti-myeloma activity. Similarly, exerts therapeutic efficacy via inducing CK1α MDS 5q. Recently, novel thalidomide analogs have been designed for better clinical efficacy, including CC-122, CC-220 CC-885. Moreover, number neo-substrates discovered. Proteolysis-targeting chimeras (PROTACs) as class bi-functional molecules increasingly used strategy target otherwise intractable cellular protein. PROTACs appear broad implications therapeutics. In this review, we summarized new generation compounds, potential neo-substrates, strategies design PROTAC drugs.