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Updated: Dec 24, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs
Published on: May 15, 2019
Crystal structure of the SALL4-pomalidomide-cereblon-DDB1 complex
Mary E Matyskiela1, Thomas Clayton2, Xinde Zheng2
1Celgene Corporation, San Diego, CA, USA. mmatyskiela@celgene.com.
Abstract:
Thalidomide-dependent degradation of the embryonic transcription factor SALL4 by the CRL4CRBN E3 ubiquitin ligase is a plausible major driver of thalidomide teratogenicity. The structure of the second zinc finger of SALL4 in complex with pomalidomide, cereblon and DDB1 reveals the molecular details of recruitment. Sequence differences and a shifted binding position relative to Ikaros offer a path to the rational design of cereblon-binding drugs with reduced teratogenic risk.
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