低酸素標的薬剤のメディシナル・ブリコラージュと次世代医薬品ボロン トレースドラッグの創生

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  • Medicinal bricolage design of hypoxia-targeting drugs and invention of boron tracedrugs as next-generation universal drugs
  • テイサンソ ヒョウテキ ヤクザイ ノ メディシナル ブリコラージュ ト ジセダイ イヤクヒン ボロン トレースドラッグ ノ ソウセイ

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Hypoxia is now considered a fundamentally important characteristic of the tumor microenvironment. A discovery of the hypoxia inducible factor（HIF）has led to a rapidly increasing understanding of the molecular mechanisms involved in tumor hypoxia. This in turn has led to the current extensive interest in the signal molecules related to tumor hypoxia as potential molecular targets for cancer therapeutics. In this paper we give a medicinal bricolage overview of recent advances in hypoxia-targeting drugs research. These hypoxia-targeting drugs include antiangiogenic- and sugar-hybrid-hypoxic cell radiosensitizers and hypoxic cytotoxins, hypoxia-targeting boron neutron capture therapy（BNCT）drugs. The evaluation of ADME-tox and pharmacokinetic properties of drugs are extremely important and essential in their discovery process and their lifetime. Traditionally, as well known traceable drugs, their radiolabeled compounds have been studied for their purposes. However, there are some inherent problems such as their half-life and regulation of experimental facilities. For the purpose of overcoming these problems and creating drugs with functions required for systems biology or emerging physiology, we designed, as a traceable nextgeneration drug model, wholly innovative drugs named“boron tracedrug,”their architecture of which were embedded boron atom in their scaffold or skeleton. These boron tracedrugs could be detected whenever and wherever you need to access in their lifetime. We called them“honnête homme”drugs. Also utilizing this specific property of boron tracedrugs, we suggested the neutron dynamic therapy（NDT）.

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