正常組織の耐容線量を高める放射線防護剤の開発

The progress of high-precision radiation therapy in recent years has been remarkable, and it has become possible to obtain a high therapeutic effect by improving dose concentration. However, in order to prevent adverse events from occurring in organs at risk, the risks of radiation injury in the normal tissues still determine the limits of the tolerable dose. Now, it is hoped that improvement of tolerable dose by a biological modification of radiation sensitivity using some molecular target drugs. Since nearly half of cancer patients have a mutation in the TP53 gene that encodes p53, p53 regulatory agents are expected to exert a selective protection of normal tissues in p53‐deficient cancer therapy. We proceeded with the exploration of 8‐quinolinol (8‐HQ) derivatives that target a zinc binding site within the p53 molecule, and found several radioprotectors controlling p53 activity. 5‐chloro‐8‐quinolinol (5CHQ), which is currently in focus, has a unique p53‐modulating activity that shifts its transactivation from proapoptotic to protective responses including enhancing p21 induction and suppressing PUMA induction. The dose-reduction factors of 5CHQ in total-body and abdominally irradiated mice were about 1.2 and 1.3, respectively. It is expected to create a new radioprotective agent that can be applied to cancer therapy.