Structural highlights
Function
A4TVL0_9PROT
Publication Abstract from PubMed
The advent of proteolysis-targeting chimaeras (PROTACs) mandates that new ligands for the recruitment of E3 ligases are discovered. The traditional immunomodulatory drugs (IMiDs) such as thalidomide and its analogues (all based on the phthalimide glutarimide core) bind to Cereblon, the substrate receptor of the CRL4A(CRBN) E3 ligase. We designed a thalidomide analogue in which the phthalimide moiety was replaced with benzotriazole, using an innovative synthesis strategy. Compared to thalidomide, the resulting "benzotriazolo thalidomide" has a similar binding mode, but improved properties, as revealed in crystallographic analyses, affinity assays and cell culture.
Replacing the phthalimide core in thalidomide with benzotriazole.,Krasavin M, Bubyrev A, Kazantsev A, Heim C, Maiwald S, Zhukovsky D, Dar'in D, Hartmann MD, Bunev A J Enzyme Inhib Med Chem. 2022 Dec;37(1):527-530. doi:, 10.1080/14756366.2021.2024525. PMID:35220840[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Krasavin M, Bubyrev A, Kazantsev A, Heim C, Maiwald S, Zhukovsky D, Dar'in D, Hartmann MD, Bunev A. Replacing the phthalimide core in thalidomide with benzotriazole. J Enzyme Inhib Med Chem. 2022 Dec;37(1):527-530. PMID:35220840 doi:10.1080/14756366.2021.2024525
