Drug development advances in human genetics‐based targets
Abstract 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, sp...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | MedComm |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/mco2.481 |
| _version_ | 1797231422380965888 |
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| author | Xiaoxia Zhang Wenjun Yu Yan Li Aiping Wang Haiqiang Cao Yuanlei Fu |
| author_facet | Xiaoxia Zhang Wenjun Yu Yan Li Aiping Wang Haiqiang Cao Yuanlei Fu |
| author_sort | Xiaoxia Zhang |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-03-07T21:52:39Z |
| format | Article |
| id | doaj.art-b36e27012b384aeaa5b420db3431b649 |
| institution | Directory Open Access Journal |
| issn | 2688-2663 |
| language | English |
| last_indexed | 2024-04-24T15:44:08Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | MedComm |
| spelling | doaj.art-b36e27012b384aeaa5b420db3431b6492024-04-01T16:35:51ZengWileyMedComm2688-26632024-02-0152n/an/a10.1002/mco2.481Drug development advances in human genetics‐based targetsXiaoxia Zhang0Wenjun Yu1Yan Li2Aiping Wang3Haiqiang Cao4Yuanlei Fu5School of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai University Yantai Shandong ChinaShandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery Yantai Shandong ChinaYantai Key Laboratory of Nanomedicine & Advanced Preparations, Yantai Institute of Materia Medica Yantai Shandong ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai University Yantai Shandong ChinaShandong Laboratory of Yantai Drug Discovery, Bohai Rim Advanced Research Institute for Drug Discovery Yantai Shandong ChinaSchool of Pharmacy, Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong Yantai University Yantai Shandong ChinaAbstract 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.https://doi.org/10.1002/mco2.481drug developmentdrug targetgenetic variationgenome‐wide association studieswhole‐exome sequencingwhole‐genome sequencing |
| spellingShingle | Xiaoxia Zhang Wenjun Yu Yan Li Aiping Wang Haiqiang Cao Yuanlei Fu Drug development advances in human genetics‐based targets MedComm drug development drug target genetic variation genome‐wide association studies whole‐exome sequencing whole‐genome sequencing |
| title | Drug development advances in human genetics‐based targets |
| title_full | Drug development advances in human genetics‐based targets |
| title_fullStr | Drug development advances in human genetics‐based targets |
| title_full_unstemmed | Drug development advances in human genetics‐based targets |
| title_short | Drug development advances in human genetics‐based targets |
| title_sort | drug development advances in human genetics based targets |
| topic | drug development drug target genetic variation genome‐wide association studies whole‐exome sequencing whole‐genome sequencing |
| url | https://doi.org/10.1002/mco2.481 |
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