Bioinspired polyhydroxamic sequestering agents for the in vivo decorporation of actinides

• Applicant: Professor Dr. Thorsten Stumpf
• Subject Area: Inorganic Molecular Chemistry - Synthesis and Characterisation ; Organic Molecular Chemistry - Synthesis and Characterisation ; Pharmacology ; Toxicology, Laboratory Medicine
• Term: since 2023
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 530101100

ActiDecorp is an multidisciplinary French-German project gathering organic, coordination and radiochemists, nuclear toxicologists, physiologists, and pharmacists from 4 complementary teams willing to design decorporating agents able to treat accidental poisoning by actinides (An = U/Np(VI), Np/Pu(IV), Am/Cm(III)). Administered alone or as cocktails, they are sought to be more efficient than Pentetate, CaNa3(DTPA), the sole drug approved by the European Pharmacopeia despite moderate efficacy for Pu-Cm and inefficiency for U-Np. Series of original chelators of various topologies possessing 2 (An(VI)) or 4 (An(III/IV)) cyclic hydroxamate binding units and their complexes (An, surrogates, biometals) will be prepared and their structures, binding thermodynamics and kinetics studied in-depth. Relying on speciation calculations, standardized An-binding assays in serum and in-cellulo toxicity studies, the identified leads will enter preclinical dose-response decorporation test with rodents (rats).

• DFG Programme: Research Grants
• International Connection: France
• Cooperation Partners: Dr. Jean-Claude Chambron; Professor Dr. Michel Meyer; Dr. Guillaume Phan