2. Academic Validation
  3. Inhibition of p53-Murine Double Minute 2 (MDM2) Interactions with 3,3'-Spirocyclopentene Oxindole Derivatives

Inhibition of p53-Murine Double Minute 2 (MDM2) Interactions with 3,3'-Spirocyclopentene Oxindole Derivatives

  • J Med Chem. 2018 Oct 25;61(20):9386-9392. doi: 10.1021/acs.jmedchem.8b01137.
Maxime Gicquel 1,  Catherine Gomez 1,  Maria Concepcion Garcia Alvarez 1,  Olivier Pamlard 1,  Vincent Guérineau 1,  Eric Jacquet 1,  Jérôme Bignon 1,  Arnaud Voituriez 1,  Angela Marinetti 1
Affiliations

Affiliation

  • 1 Institut de Chimie des Substances Naturelles, CNRS UPR 2301, Université Paris-Sud, Université Paris-Saclay , 1, Avenue de la Terrasse , 91198 Gif-sur-Yvette , France.
PMID: 30221935 DOI: 10.1021/acs.jmedchem.8b01137
Abstract

3,3'-Spirocyclopentene oxindoles structurally related to Wang's spiropyrrolidine oxindoles have been highlighted as a new class of antiproliferative agents against Cancer cell lines with wild-type p53 status (IC50 up to 0.96 μM on SJSA-1 and 2.9 μM in HCT116 p53-wt). Inhibition of the MDM2-p53 interactions has been demonstrated through in vitro HTRF assays (IC50 up to 3.1 nM), while Western blot analysis showed activation of p53 selectively in HCT116 Cancer cell lines with wild-type p53.

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