2,30-Bis(10H-indole) heterocycles: New p53/MDM2/MDMX antagonists.

Constantinos G. Neochoritis, Kan Wang, Natalia Estrada-Ortiz, Eberhardt Herdtweck, Katarzyna Kubica, Aleksandra Twarda, Krzysztof M. Zak, Tad A. Holak, Alexander Dömling

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17 Citations (Scopus)

Abstract

The protein–protein interaction of p53 and MDM2/X is a promising non genotoxic anticancer target. A rapid and efficient methodology was developed to synthesize the 2,3′-bis(1′H-indole) heterocyclic scaffold 2 as ester, acid and amide derivatives. Their binding affinity with MDM2 was evaluated using both fluorescence polarization (FP) assay and HSQC experiments, indicating good inhibition and a perfect starting point for further optimizations.
Original languageEnglish
Pages (from-to)5661-5666
Number of pages6
JournalBioorganic and Medicinal Chemistry Letters
Volume25
Issue number24
DOIs
Publication statusPublished - 15-Dec-2015

Keywords

  • DISCOVERY
  • ACYLATION
  • TRANSIENT PROTEIN STATES
  • MDM2-P53 INTERACTION
  • P53
  • INHIBITORS
  • CANCER
  • MDMX
  • DEGRADATION
  • CHEMISTRY

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