Drug development advances in human genetics-based targets
文献类型：期刊论文
| 作者 | Zhang, Xiaoxia1,2; Yu, Wenjun3; Li, Yan2; Wang, Aiping1,7; Cao, Haiqiang3,4,5,6; Fu, Yuanlei1,2,3,6 |
| 刊名 | MEDCOMM
 |
| 出版日期 | 2024-02-01 |
| 卷号 | 5期号:2页码:e481 |
| 关键词 | drug development drug target genetic variation genome-wide association studies whole-exome sequencing whole-genome sequencing |
| DOI | 10.1002/mco2.481 |
| 文献子类 | Review |
| 英文摘要 | Drug development is a long and costly process, with a high degree of uncertainty from the identification of a drug target to its market launch. Targeted drugs supported by human genetic evidence are expected to enter phase II/III clinical trials or be approved for marketing more quickly, speeding up the drug development process. Currently, genetic data and technologies such as genome-wide association studies (GWAS), whole-exome sequencing (WES), and whole-genome sequencing (WGS) have identified and validated many potential molecular targets associated with diseases. This review describes the structure, molecular biology, and drug development of human genetics-based validated beneficial loss-of-function (LOF) mutation targets (target mutations that reduce disease incidence) over the past decade. The feasibility of eight beneficial LOF mutation targets (PCSK9, ANGPTL3, ASGR1, HSD17B13, KHK, CIDEB, GPR75, and INHBE) as targets for drug discovery is mainly emphasized, and their research prospects and challenges are discussed. In conclusion, we expect that this review will inspire more researchers to use human genetics and genomics to support the discovery of novel therapeutic drugs and the direction of clinical development, which will contribute to the development of new drug discovery and drug repurposing.Progress in drug discovery based on targets with favorable LOF variants identified by WES, WGS, and GWAS. Targets primarily include PCSK9, ANGPTL3, HSD17B13, KHK, ASGR1, GPR75, CIDEB, and INHBE. Drug types primarily include small molecules, monoclonal antibodies, RNAi, and CRISPR gene editing therapies. The timeline is determined by the status of the target's current investigational drugs. image |
| WOS关键词 | OF-FUNCTION MUTATIONS ; ANGIOPOIETIN-LIKE PROTEIN-3 ; GENOME-WIDE ASSOCIATION ; ANTISENSE OLIGONUCLEOTIDES ; HEPATOCELLULAR-CARCINOMA ; HEPATIC LIPOGENESIS ; ANGPTL3 DEFICIENCY ; LOW LDL ; PCSK9 ; FRUCTOSE |
| WOS研究方向 | Medicine, Research & Experimental |
| 语种 | 英语 |
| WOS记录号 | WOS:001159758500001 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/317024]  |
| 专题 | 新药研究国家重点实验室 |
| 通讯作者 | Wang, Aiping; Cao, Haiqiang; Fu, Yuanlei |
| 作者单位 | 1.Yantai Univ, Collaborat Innovat Ctr Adv Drug Delivery Syst & Bi, Key Lab Mol Pharmacol & Drug Evaluat,Minist Educ, Sch Pharm, Yantai, Shandong, Peoples R China 2.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai, Shandong, Peoples R China 3.Bohai Rim Adv Res Inst Drug Discovery, Shandong Lab Yantai Drug Discovery, Yantai, Shandong, Peoples R China 4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai, Peoples R China 5.Shanghai Inst Mat Med, Chinese Acad Sci, Ctr Pharmaceut, Shanghai, Peoples R China 6.Yantai Inst Mat Med, Yantai Key Lab Nanomed & Adv Preparat, Yantai 264000, Shandong, Peoples R China 7.Yantai Univ, Sch Pharm, 30 Qingquan Rd, Yantai 264005, Shandong, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Xiaoxia,Yu, Wenjun,Li, Yan,et al. Drug development advances in human genetics-based targets[J]. MEDCOMM,2024,5(2):e481. |
| APA | Zhang, Xiaoxia,Yu, Wenjun,Li, Yan,Wang, Aiping,Cao, Haiqiang,&Fu, Yuanlei.(2024).Drug development advances in human genetics-based targets.MEDCOMM,5(2),e481. |
| MLA | Zhang, Xiaoxia,et al."Drug development advances in human genetics-based targets".MEDCOMM 5.2(2024):e481. |
入库方式： OAI收割
来源：上海药物研究所
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