Wondrak Georg T
Arizona Cancer Center, University of Arizona, Department of Pharmacology and Toxicology, College of Pharmacy, 1515 North Campbell Avenue, Tucson, AZ 85724, USA.
Curr Opin Investig Drugs. 2007 May;8(5):390-400.
Photoaging and photocarcinogenesis are the two Janus faces of skin photodamage. Reactivity-based design of prototype agents that antagonize, modulate and reverse the chemistry of skin photodamage holds promise in delivering unprecedented therapeutic benefit. In contrast to structure-based approaches that use selective ligands to target macromolecules, reactivity-based drug discovery uses chemical reagents as therapeutics to target reactive chemical species as key mediators of skin photo-oxidative stress. The following classes of reactivity-based agents for skin photoprotection can be distinguished based on their mechanism of action: direct antagonists of photo-oxidative stress (sunscreens, quenchers of photo-excited states, antioxidants, redox modulators and glycation inhibitors) and skin photo-adaptation inducers (nuclear factor erythroid 2-related factor 2 [Nrf2] activators, heat-shock response inducers and metallothionein inducers).
光老化和光致癌作用是皮肤光损伤的两个方面。基于反应性设计的原型药物可对抗、调节和逆转皮肤光损伤的化学过程，有望带来前所未有的治疗益处。与使用选择性配体靶向大分子的基于结构的方法不同，基于反应性的药物发现使用化学试剂作为治疗药物，以靶向作为皮肤光氧化应激关键介质的反应性化学物质。基于作用机制，可区分出以下几类用于皮肤光保护的基于反应性的药物：光氧化应激的直接拮抗剂（防晒霜、光激发态猝灭剂、抗氧化剂、氧化还原调节剂和糖基化抑制剂）以及皮肤光适应诱导剂（核因子红细胞2相关因子2 [Nrf2] 激活剂、热休克反应诱导剂和金属硫蛋白诱导剂）。
