Screening multicomponent reactions for X-linked inhibitor of apoptosis-baculoviral inhibitor of apoptosis protein repeats domain binder

Monfardini, I., Huang, J-W., Beck, B., Cellitti, J. F., Pellecchia, M. & Dömling, A., 10-Feb-2011, In : Journal of Medicinal Chemistry. 54, 3, p. 890-900 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • Ilaria Monfardini
  • Jui-Wen Huang
  • Barbara Beck
  • Jason F Cellitti
  • Maurizio Pellecchia
  • Alexander Dömling

We report a second example of a general reaction screening approach to discover low molecular weight inhibitors of protein protein interactions. On the basis of the known pharmacophore model of SMAC mimetics, we predicted several inhibitors based on four different multicomponent reactions. The predicted inhibitors were subsequently synthesized, tested, and found to bind to the antiapoptotic protein X-linked inhibitor of apoptosis protein (XIAP) and showed cellular activity. Also the compounds are currently not highly potent. They could form a starting point for future medicinal chemistry optimization.

Original languageEnglish
Pages (from-to)890-900
Number of pages11
JournalJournal of Medicinal Chemistry
Issue number3
Publication statusPublished - 10-Feb-2011


  • Amino Acid Motifs, Amino Acid Sequence, Antineoplastic Agents, Cell Line, Tumor, Cell Survival, Databases, Factual, Drug Screening Assays, Antitumor, Humans, Models, Molecular, Peptidomimetics, Piperazines, Protein Binding, Stereoisomerism, Structure-Activity Relationship, Tetrazoles, Thiazoles, Thiazolidines, X-Linked Inhibitor of Apoptosis Protein

ID: 13780602