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)

*Corresponding author for this work

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Abstract

Due to its anti-angiogenic 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 anti-angiogenic 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 anti-angiogenic thalidomide analogs can bind cereblon, and multiple targets and mechanisms of action may be involved.
Original languageEnglish
Article number5683
Number of pages18
JournalMolecules
Volume25
Issue number23
DOIs
Publication statusPublished - 2 Dec 2020

Keywords

  • angiogenesis
  • thalidomide
  • SAR
  • cereblon
  • docking
  • structure-activity
  • relationships
  • structure–activity relationships

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