Recent Advances in Developing Inhibitors for Hypoxia-Inducible Factor Prolyl Hydroxylases and Their Therapeutic Implications

Molecules

So Yeon Kim¹  Eun Gyeong Yang¹ 

[1] Center for Theragnosis, Biomedical Research Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Korea;

关键词: prolyl hydroxylase (PHD) inhibitor;    hypoxia-inducible factor (HIF);    structure-based drug design (SBDD);    high-throughput screening (HTS);   

DOI  :  10.3390/molecules201119717

来源: mdpi

【 摘 要 】

Hypoxia-inducible factor (HIF) prolyl hydroxylases (PHDs) are members of the 2-oxoglutarate dependent non-heme iron dioxygenases. Due to their physiological roles in regulation of HIF-1α stability, many efforts have been focused on searching for selective PHD inhibitors to control HIF-1α levels for therapeutic applications. In this review, we first describe the structure of PHD2 as a molecular basis for structure-based drug design (SBDD) and various experimental methods developed for measuring PHD activity. We further discuss the current status of the development of PHD inhibitors enabled by combining SBDD approaches with high-throughput screening. Finally, we highlight the clinical implications of small molecule PHD inhibitors.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.