新靶点GDF15的作用机制及其相关药物研发现状  

The mechanism of action of new target GDF15 and current research and development of related drugs

作　　者：强昊 孙明霞 王洪建 朱婷婷 吉腾飞 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)

机构地区：[1]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

出　　处：《药学学报》2021年第10期2728-2734,共7页Acta Pharmaceutica Sinica

基　　金：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)。

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 factorβ,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 receptorα-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。Growth differentiation factor 15(GDF15)is an endocrine hormone that belongs to the transforming growth factorβ(TGFβ)superfamily,which plays a role by binding to the glial cell line derived neurotrophic factor(GDNF)-family receptorα-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.

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 

分 类 号：R964[医药卫生—药理学]