Hancock Wayne W
Division of Transplant Immunology, Department of Pathology and Laboratory Medicine, 916B Abramson Research Center, Children's Hospital of Philadelphia and University of Pennsylvania School of Medicine, Philadelphia, PA 19104-4318, USA.
Handb Exp Pharmacol. 2011;206:103-23. doi: 10.1007/978-3-642-21631-2_6.
While there are currently more than 70 ongoing clinical trials of inhibitors of so-called classical HDACs (HDACi) as anticancer therapies, given their potency as antiproliferative and angiostatic agents, HDACi also have considerable therapeutic potential as anti-inflammatory and immunosuppressive drugs. The utility of HDACi as anti-inflammatory agents is dependent upon their proving safe and effective in experimental models. Current pan-HDACi compounds are not well suited to this role, given the broad distribution of target HDACs and their complex and multifaceted mechanisms of action. In contrast, the development of isoform-selective HDACi may provide important new tools for therapy in autoimmunity and transplantation. This chapter discusses which HDACs are worthwhile targets in inflammation and progress toward their therapeutic inhibition, including the use of HDAC subclass and isoform-selective HDACi to promote the functions of Foxp3+ T regulatory cells.
目前有70多项正在进行的临床试验，将所谓经典组蛋白去乙酰化酶（HDAC）抑制剂作为抗癌疗法。鉴于其作为抗增殖和血管生成抑制剂的效力，HDAC抑制剂作为抗炎和免疫抑制药物也具有相当大的治疗潜力。HDAC抑制剂作为抗炎药物的效用取决于它们在实验模型中证明是安全有效的。鉴于目标HDAC分布广泛及其复杂多面的作用机制，目前的泛HDAC抑制剂化合物不太适合这一角色。相比之下，亚型选择性HDAC抑制剂的开发可能为自身免疫和移植治疗提供重要的新工具。本章讨论了哪些HDAC是炎症中值得靶向的目标以及在治疗性抑制方面取得的进展，包括使用HDAC亚类和亚型选择性HDAC抑制剂来促进Foxp3 + T调节细胞的功能。
