Antiangiogenic activity and in silico cereblon binding analysis of novel thalidomide analogs

Megan L. Peach, Shaunna L. Beedie, Cindy H. Chau, Matthew K. Collins, Suzana Markolovic, Weiming Luo, David Tweedie, Christian Steinebach, Nigel H. Greig, Michael Gütschow, Neil Vargesson, Marc C. Nicklaus, William D. Figg*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

12 Scopus citations

Abstract

Due to its antiangiogenic and anti-immunomodulatory activity, thalidomide continues to be of clinical interest despite its teratogenic actions, and efforts to synthesize safer, clinically active thalidomide analogs are continually underway. In this study, a cohort of 27 chemically diverse thalidomide analogs was evaluated for antiangiogenic activity in an ex vivo rat aorta ring assay. The protein cereblon has been identified as the target for thalidomide, and in silico pharmacophore analysis and molecular docking with a crystal structure of human cereblon were used to investigate the cereblon binding abilities of the thalidomide analogs. The results suggest that not all antiangiogenic thalidomide analogs can bind cereblon, and multiple targets and mechanisms of action may be involved.

Original languageEnglish
Article number5683
JournalMolecules
Volume25
Issue number23
DOIs
StatePublished - 1 Dec 2020
Externally publishedYes

Keywords

  • Angiogenesis
  • Cereblon
  • Docking
  • Structure–activity relationships
  • Thalidomide

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