Promising therapeutic strategies to eliminate cancer cells consist of selective agonists of apoptosis, a programmed cell death. The activation of the death receptor 5 (DR5) by its ligand TRAIL plays a major role in this process and it is an attractive and safe pharmacological target.
Gelin Wang, University of Texas Southwestern Medical Center, USA, and colleagues synthetized the first chemical compound targeting DR5. The scientists demonstrated that the new drug, (Z)-5-(5-[(3-[4-bromophenyl]-2-imino-4-oxothiazolidin-5-ylidene)methyl]furan-2-yl)isoindoline-1,3-dione or Bioymifi (pictured), acts as a TRAIL mimetic.
Similarly to TRAIL, this small molecule directly binds to the extracellular domain of the DR5 receptors and induces their aggregation, a mandatory step for the following activation of the apoptotic program. As a consequence, Bioymifi promotes cell death in various human cancer cells.
- Small-molecule activation of the TRAIL receptor DR5 in human cancer cells,
G. Wang, X. Wang, H. Yu, S. Wei, N. Williams, D. L. Holmes, R. Halfmann, J. Naidoo, L. Wang, L. Li, S. Chen, P. Harran, X. Lei, X. Wang,
Nat. Chem. Biol. 2012.