IEA So-Pretty

French-Singaporean International Emerging Action in chemistry.

IEA SO-PRETTY
2020-2021
Contact:
Dr. Hélène Bertrand
helene.bertrand(at)ens.psl.eu
Prof. Wee Han Ang
ang.weehan(at)nus.edu.sg

IEA SO-PRETTY
News

Introduction

The IEA SO-PRETTY (International Emerging Action SODmimics-Oxaliplatine Platinum(IV) conjugates with REduced ToxiciTY), managed by Dr. Hélène Bertrand (CNRS, Laboratoire des Biomolécules, Sorbonne Université – Ecole Normale Supérieure – Paris Sciences et Lettres) in collaboration with Institut Cochin (Prof. Frédéric Batteux and Prof. Romain Coriat) and the departments of Chemistry (Prof. Wee Han Ang) and Pharmacy (Prof. Giorgia Pastorin) of National University of Singapore will be effective in 2020 and 2021.

Missions and research themes

Pt anticancer drugs are efficient chemotherapeutic agents extensively used in clinics but their toxicity limits their efficacy. These compounds, such as Oxaliplatin (Ox), produce a burst of intracellular oxidative stress leading to cancer cells’ death through a higher sensitivity to the increased oxidative stress. Ox is an efficient chemotherapeutic agent widely used in clinics with a main indication in metastatic colorectal cancer. However, a major limiting factor in its administration is its toxicity and in particular the peripheral neuropathy it induces, which pathophysiology has been linked to the oxidative burst generated. Several modulators of the redox balance have demonstrated interesting results in counteracting Ox-induced neurotoxicity. In this context, we wish to evaluate the relevance of small metallic complexes, mimics of Superoxide dismutase (SOD) a metalloenzyme involved in oxidative stress management, in clinical settings to answer the critical need of increasing Ox therapeutic index.

MAIN projects of research

 We have recently shown that the combined treatment of oxaliplatin (Ox) with a bioinspired SOD mimic developed in our lab, in mice, prevented the appearance of sensitive axonal neuropathy and neuromuscular disorders induced by Ox. In this project, we will develop the first covalent conjugates between SOD mimics and Ox. By design of these prodrugs, we will control the intracellular activity of both active components and will optimize their cellular and tumoral targeting to generate efficient anticancer agents with a reduced toxicity.

institutions and laboratories involved

France:
• Dr Hélène Bertrand (Laboratoire des Biomolécules, CNRS-Sorbonne Université – ENS-PSL)

• Prof. Frédéric Batteux and Prof. Romain Coriat (Institut Cochin).

Singapore:
• Prof. Wee Han Ang (Department of Chemistry, NUS) ; Prof. Giorgia Pastorin (Department of Pharmacy, NUS).