News Releases & Research Results Controlling the actions and physical properties of drugs by metal-catalyzed reactions in vivo: a new direction in designing prodrugs

The results of the collaborative research and development (R&D) project conducted by Chief Scientist Katsunori Tanaka (concurrently serving as Professor of the Department of Chemical Science and Engineering, Tokyo Institute of Technology) and Researcher Kenward Von of the Biofunctional Synthetic Chemistry Laboratory, RIKEN Cluster for Pioneering Research, and others.

• The research group successfully developed transition-metal-catalyzed (*1) reactions enabling the selective release of drugs in target tissues, including cancer cells.
  (*1) Transition-metal catalysts refer to catalysts containing transition metal elements belonging to Groups 3–11 of the periodic table.
• Specifically, they developed the "2-alkynylbenzamide (Ayba) moiety" protective groups that can be introduced into the amino group of a drug compound and succeeded in metal-catalyzed reaction-mediated control of drug activity to kill cancer cells by adjustment of the structure of the Ayba group and the type of metal catalyst.
• The results of R&D should facilitate the establishment of a novel technique for prodrugs (*2), which are intended to control the actions and physical properties (cell membrane permeability) of drugs by reactions in vivo.
  (*2) A prodrug is a drug that is designed to be converted into an active drug compound as a result of biological reactions at its target site.

This program was conducted with support of the Science and Technology Platform Program for Advanced Biological Medicine by AMED.

The results of this R&D project were published online in Chemical Science, a scientific journal, on September 2.

Kenward Vong, et al. Bioorthogonal release of anticancer drugs via gold-triggered 2-alkynylbenzamide cyclization Chemical Science
DOI：10.1039/d0sc04329j