ArticleChemical biology & drug design2026
Design, Synthesis, Biological Studies and Putative Binding Mode of Novel Benzotriazolothalidomide Derivatives as Cereblon Ligands.
Article in Chemical biology & drug design, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Targeted protein degradation (TPD) represents a new paradigm in drug discovery, encompassing several innovative strategies like proteolysis targeting chimeras (PROTACs). PROTACs work by linking the target protein of interest (POI) to an E3 ubiquitin ligase, marking it for ubiquitination, and subsequent degradation by the proteasome. The ligand space of E3 ligase cereblon (CRBN) mostly includes phthalimide-based thalidomide 1 and its analogs, commonly known as cereblon E3 ligase modulators (CELMoDs) which have been approved for the treatment of multiple subtypes of non-Hodgkin's lymphoma (NHL). Recently, benzotriazolo thalidomide (4) was reported which displayed similar binding mode like thalidomide, having relatively stronger binding affinity. Towards our aim of identifying new generation CRBN binding ligands, which can have use either in PROTAC or CELMoD chemical space, systematic design and SAR studies around 4, synthesis, biological, and docking experiments to understand putative binding mode have been carried out. As a result, a few compounds were identified as potent CRBN ligands, including compound 13 having an IC
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