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.
- structure–activity relationships