Nanjing Medical University, The First Affiliated Hospital, Research Division of Clinical Pharmacology , 300 Guangzhou Road, Nanjing, Jiangsu Province, 210029 , China.
Expert Opin Ther Pat. 2013 Nov;23(11):1435-49. doi: 10.1517/13543776.2013.828695. Epub 2013 Aug 19.
FK506-binding protein 12 (FKBP12) is an endogenous protein with peptidyl-prolyl isomerase (PPIase) activity. Natural compounds FK506, rapamycin and ascomycin, are FKBP12 ligands used for treating organ transplant rejection and other diseases. Small ligands that also interact with FKBP12 are designed and synthetized based on the natural ligands. This suggests that targeting FKBP12 has potential in the treatment of multiple diseases.
This article describes the features of FKBP12 and the therapeutic actions of agents targeting FKBP12 reported in the published articles and patents.
The multiple functions of FKBP12 cause side effects during therapy with FKBP12 ligands. The interaction between FKBP12 and other receptors should be explored to guide their use as drugs in the clinical setting. In addition, the neuroprotective mechanism of small-molecule FKBP12 ligands needs further study in order to develop them as novel drugs for treating neurological disorders.
FK506 结合蛋白 12（FKBP12）是一种具有肽基脯氨酰顺反异构酶（PPIase）活性的内源性蛋白。天然化合物 FK506、雷帕霉素和 Aspergillus niger 菌素是用于治疗器官移植排斥反应和其他疾病的 FKBP12 配体。根据天然配体设计和合成了与 FKBP12 相互作用的小分子配体。这表明靶向 FKBP12 在治疗多种疾病方面具有潜力。
本文描述了 FKBP12 的特征以及已发表文章和专利中报道的靶向 FKBP12 的药物的治疗作用。
FKBP12 配体治疗过程中，FKBP12 的多种功能会导致副作用。应探索 FKBP12 与其他受体的相互作用，以指导其在临床环境中作为药物使用。此外，小分子 FKBP12 配体的神经保护机制需要进一步研究，以便将其开发为治疗神经退行性疾病的新型药物。
