药学学报, 2021, 56(10): 2728-2734
引用本文:
强昊, 孙明霞, 王洪建, 朱婷婷, 吉腾飞*. 新靶点GDF15的作用机制及其相关药物研发现状[J]. 药学学报, 2021, 56(10): 2728-2734.
QIANG Hao, SUN Ming-xia, WANG Hong-jian, ZHU Ting-ting, JI Teng-fei*. The mechanism of action of new target GDF15 and current research and development of related drugs[J]. Acta Pharmaceutica Sinica, 2021, 56(10): 2728-2734.

新靶点GDF15的作用机制及其相关药物研发现状
强昊, 孙明霞, 王洪建, 朱婷婷, 吉腾飞*
中国医学科学院、北京协和医学院药物研究所, 天然药物活性物质与功能国家重点实验室, 北京 100050
摘要:
生长分化因子15(growth differentiation factor 15,GDF15)是一种内分泌激素,是转化生长因子β(transforming growth factor β,TGFβ)超家族成员,与胶质细胞源性神经营养因子(glial cell line derived neurotrophic factor,GDNF)家族受体α样(GDNF-family receptor α-like,GFRAL)-转染重排(rearranged during transfection,RET)异源二聚体受体结合而发挥作用。GDF15作为肥胖、糖尿病、肿瘤、非酒精性脂肪性肝病、缺血性疾病等的生物标志物已成为新药研发的新靶点。目前,世界各制药企业均开展了以GDF15为全新治疗靶点的药物研究,涉及肥胖、肿瘤及厌食综合征等诸多领域,本文综合分析了GDF15靶点的优缺点,探讨并客观评价了基于GDF15的新药研发,将为相关创新药物发现提供科学依据。
关键词:    生长分化因子15      治疗靶点      药物研发      厌食      肥胖      生物标志物     
The mechanism of action of new target GDF15 and current research and development of related drugs
QIANG Hao, SUN Ming-xia, WANG Hong-jian, ZHU Ting-ting, JI Teng-fei*
State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China
Abstract:
Growth differentiation factor 15 (GDF15) is an endocrine hormone that belongs to the transforming growth factor β (TGFβ) superfamily, which plays a role by binding to the glial cell line derived neurotrophic factor (GDNF)-family receptor α-like (GFRAL)-rearranged during transfection (RET) heterodimer receptor. A number of studies have confirmed that GDF15, as a biomarker for obesity, diabetes, tumors, non-alcoholic fatty liver disease, ischemic diseases, and so on, has become a new target for new drug discovery. At present, pharmaceutical companies around the world are carrying out drug discovery with GDF15 as a new therapeutic target involving many therapeutic areas such as anti-obesity, anti-tumor, and treatment of anorexia syndrome. Comprehensive analysis of the advantages and disadvantages of the GDF15 target, discussion, and objective evaluation of research and development of new drugs based on GDF15 will provide a scientific basis for the discovery of innovative drugs that could relieve the human suffering from illness.
Key words:    growth differentiation factor 15    therapeutic target    research and development of drug    anorexia    obesity    biomarker   
收稿日期: 2021-05-05
DOI: 10.16438/j.0513-4870.2021-0675
基金项目: 中药材产业精准扶贫关键技术协同创新团队资助项目(2019-I2M-3-001).
通讯作者: 吉腾飞,Tel:86-10-63165226,E-mail:jitf@imm.ac.cn
Email: jitf@imm.ac.cn
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