Prognostic significance of NUAK1 and its association with immune infiltration in stomach adenocarcinoma DOI Creative Commons
Xin Ni, Fan Pan, Y Lang

и другие.

Discover Oncology, Год журнала: 2024, Номер 15(1)

Опубликована: Дек. 18, 2024

Stomach adenocarcinoma (STAD) represents a significant global health burden, accounting for considerable proportion of cancer-related mortalities, and NUAK1, protein kinase, plays crucial role in cellular metabolism, cell cycle regulation, migration, tumor progression. However, its relationship with prognosis immune infiltration STAD has not been thoroughly investigated. RNA sequencing data from the Cancer Genome Atlas (TCGA) Genotypic Tissue Expression Project (GTEx) databases were employed to assess disparities NUAK1 expression between tumour normal tissues. Additionally, we investigated correlation patient prognosis, addition level infiltration. The potential functions elucidated through an examination Gene Ontology (GO) Encyclopedia, Kyoto Encyclopedia Genes Genomes (KEGG), enrichment analysis (GSEA). GeneMANIA was used validate nuak1-related genes. Our demonstrated that tissues exhibited notable disparity observed tissues, elevated levels detected We database identify functionally similar genes significantly higher some unpaired group samples. An found correlate poorer overall survival (OS), disease-specific (DSS), progression-free intervals (PFI). indicated positive various tumor-infiltrating cells, while negative T helper 17(Th17) cells. Furthermore, conducted relevant biological features pathways. are increased STAD, this heightened correlates diminished OS, DSS, PFI among affected patients. These observations indicate function as prognostic biomarker may represent viable therapeutic target intervention management.

Язык: Английский

Development of the Pyrido[2,3-d]pyrimidin-7(8H)-one Scaffold toward Potent and Selective NUAK1 Inhibitors DOI Creative Commons
Timothy P. C. Rooney, Gregory G. Aldred,

David Winpenny

и другие.

ACS Medicinal Chemistry Letters, Год журнала: 2025, Номер unknown

Опубликована: Янв. 25, 2025

The protein kinase NUAK1 has been implicated in various biological functions including cell adhesion, migration and proliferation. Genetic reduction of expression notably shown to lower total levels human tau a tauopathy mouse model, identifying this as potential therapeutic target for neurodegenerative disease. In paper, we describe improvement the potency, kinase-selectivity pharmacokinetic properties brain-penetrant but unselective CDK4/CDK6/NUAK1 inhibitor ON123300. Through scaffold-optimization approach have identified different chemotypes delivering inhibition with improved potency selectivity over CDK kinases compared We present ADME profiling vivo data these compounds.

Язык: Английский

Процитировано

0
A special issue of Essays in Biochemistry on AMPK and AMPK-related kinases DOI Creative Commons
Ian P. Salt, David Carling

Essays in Biochemistry, Год журнала: 2024, Номер 68(3), С. 269 - 271

Опубликована: Ноя. 1, 2024

Abstract In eukaryotic cells, AMP-activated protein kinase (AMPK) plays a central role in responding to nutrient limitation by switching-off ATP-consuming (anabolic) pathways and switching-on ATP generating (catabolic) pathways. Over the last 30 years or so, considerable body of research has been carried out that provided us with wealth knowledge regarding regulation AMPK. Despite this, there is still much learn about AMPK field remains highly active, many groups around world continuing explore new roles for AMPK, providing insight into its biological function. This review series was inspired recent AMPK-focused meetings Scotland (2022) Australia (2023) draws on some presented at those meetings.

Язык: Английский

Процитировано

0
Prognostic significance of NUAK1 and its association with immune infiltration in stomach adenocarcinoma DOI Creative Commons
Xin Ni, Fan Pan, Y Lang

и другие.

Discover Oncology, Год журнала: 2024, Номер 15(1)

Опубликована: Дек. 18, 2024

Stomach adenocarcinoma (STAD) represents a significant global health burden, accounting for considerable proportion of cancer-related mortalities, and NUAK1, protein kinase, plays crucial role in cellular metabolism, cell cycle regulation, migration, tumor progression. However, its relationship with prognosis immune infiltration STAD has not been thoroughly investigated. RNA sequencing data from the Cancer Genome Atlas (TCGA) Genotypic Tissue Expression Project (GTEx) databases were employed to assess disparities NUAK1 expression between tumour normal tissues. Additionally, we investigated correlation patient prognosis, addition level infiltration. The potential functions elucidated through an examination Gene Ontology (GO) Encyclopedia, Kyoto Encyclopedia Genes Genomes (KEGG), enrichment analysis (GSEA). GeneMANIA was used validate nuak1-related genes. Our demonstrated that tissues exhibited notable disparity observed tissues, elevated levels detected We database identify functionally similar genes significantly higher some unpaired group samples. An found correlate poorer overall survival (OS), disease-specific (DSS), progression-free intervals (PFI). indicated positive various tumor-infiltrating cells, while negative T helper 17(Th17) cells. Furthermore, conducted relevant biological features pathways. are increased STAD, this heightened correlates diminished OS, DSS, PFI among affected patients. These observations indicate function as prognostic biomarker may represent viable therapeutic target intervention management.

Язык: Английский

Процитировано

0