The association between circulatory, local pancreatic PCSK9 and type 2 diabetes mellitus: The effects of antidiabetic drugs on PCSK9

Lu, Fengyuan; Li, En; Yang, Xiaoyu

doi:10.1016/j.heliyon.2023.e19371

Cited by 1 publication

(1 citation statement)

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“…PCSK9 also binds to CD36 to promote platelet activation and thrombosis and to reduce fatty acid uptake and TG accumulation in tissues 86 . A significant correlation has been found between PCSK9 and glucose metabolism, 87 but studies linking PCSK9 LOF variants to the risk of developing diabetes are conflicting 88,89 . PCSK9 may also be involved in the pathogenesis of fatty liver disease.…”

Section: Drug Development Of Targets Based On Gwas Wgs and Wes Discov...mentioning

confidence: 99%

Drug development advances in human genetics‐based targets

Zhang,

Yu,

et al. 2024

MedComm

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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.

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Section: Drug Development Of Targets Based On Gwas Wgs and Wes Discov...mentioning

confidence: 99%