TFC-1326 Compound Reduces Clinical Signs of Skin Aging. Evidence From In Vitro Human Adipose and Skin Models and Pilot Clinical Trial.

Background: Anti-freeze Glycoproteins (AFGPs) were described to preserve biological materials and protect them from different stresses.

Aims: The effects of a synthetic anti-freeze glycoprotein-based compound, TFC-1326, on human skin quality and its biological actions were studied.

Methods: The effects of various concentrations of TFC-1326 on the biology of human preadipocytes, differentiated in the proinflammatory microenvironment, and on human fibroblasts grown in coculture with human mature adipocytes or monocultured in stress conditions were investigated in, in vitro studies.

Transcription-associated topoisomerase 2α (TOP2A) activity is a major effector of cytotoxicity induced by G-quadruplex ligands.

G-quadruplexes (G4) are non-canonical DNA structures found in the genome of most species including human. Small molecules stabilizing these structures, called G4 ligands, have been identified and, for some of them, shown to induce cytotoxic DNA double-strand breaks. Through the use of an unbiased genetic approach, we identify here topoisomerase 2α (TOP2A) as a major effector of cytotoxicity induced by two clastogenic G4 ligands, pyridostatin and CX-5461, the latter molecule currently undergoing phase I/II clinical trials in oncology.