The NAD⁺-dependent protein lysine deacylases of the Sirtuin family regulate various physiological functions, from energy metabolism to stress responses. The human Sirtuin isoforms, SIRT1–7, are considered attractive therapeutic targets for aging-related diseases, such as type 2 diabetes, inflammatory diseases and neurodegenerative disorders. We review the status of Sirtuin-targeted drug discovery and development. Potent and selective pharmacological Sirt1 activators and inhibitors are available, and initial clinical trials have been carried out. Several promising inhibitors and activators have also been described for other isoforms. Progress in understanding the mechanisms of Sirtuin modulation by such compounds provides a rational basis for further drug development.

Sirtuin家族的NAD ⁺依赖性蛋白赖氨酸脱酰基调节各种生理功能，从能量代谢到应激反应。人类Sirtuin亚型SIRT1–7被认为是与衰老相关的疾病（如2型糖尿病，炎性疾病和神经退行性疾病）的有吸引力的治疗靶标。我们回顾了针对Sirtuin的药物发现和开发的状态。可以使用有效的选择性药理Sirt1激活剂和抑制剂，并且已经进行了初步的临床试验。对于其他同工型，也已经描述了几种有希望的抑制剂和活化剂。对此类化合物对Sirtuin调节机制的了解的进展为进一步药物开发提供了合理的基础。