Biological Investigation of a Water-Soluble Isoginkgetin-Phosphate Analogue, Targeting the Spliceosome with In Vivo Antitumor Activity

  • J Med Chem. 2022 Mar 24;65(6):4633-4648. doi: 10.1021/acs.jmedchem.1c01654.
Boris Letribot  1 ,  Megane Nascimento  2 ,  Giulia Cerrato  3 ,  Romain Darrigrand  2 ,  Valerie Salgues  2 ,  Dolor Renko  1 ,  Alain Pruvost  4 ,  Mouad Alami  1 ,  Samir Messaoudi  1 ,  Sebastien Apcher  2
Affiliations
  • 1. Université Paris-Saclay, CNRS, BioCIS, Châtenay-Malabry 92290, France.
  • 2. Université Paris-Saclay, Institut Gustave Roussy, Inserm, Immunologie des tumeurs et Immunothérapie, Villejuif 94805, France.
  • 3. Université Paris-Saclay, Institut Gustave Roussy, Metabolomics and Cell Biology Platforms, Villejuif 94805, France.
  • 4. Université Paris-Saclay, CEA, INRAE, Département Médicaments et Technologies pour La Santé, SPI, Gif-sur-Yvette 91191, France.
PMID: 35235336 DOI: 10.1021/acs.jmedchem.1c01654
Abstract

The first total synthesis of the natural product Isoginkgetin as well as four water-soluble Isoginkgetin-phosphate analogues is reported herein. Moreover, the full study of the IP2 phosphate analogue with respect to pharmacological properties (metabolic and plasmatic stabilities, pharmacokinetic, off-target, etc.) as well as in vitro and in vivo biological activities are disclosed herein.

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