N6-Methyladenosine Methyltransferase Component KIAA1429 Is a Potential Target of Cancer Therapy DOI Creative Commons
Junjun Huang, Jihua Guo, Rong Jia

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(10), P. 1319 - 1319

Published: Oct. 17, 2024

N6-methyladenosine (m

Death-associated protein kinase 1 as a therapeutic target for Alzheimer's disease DOI Creative Commons
Tao Zhang, Byeong Mo Kim, Tae Ho Lee

et al.

Translational Neurodegeneration, Journal Year: 2024, Volume and Issue: 13(1)

Published: Jan. 9, 2024

Alzheimer's disease (AD) is the most prevalent form of dementia in elderly and represents a major clinical challenge ageing society. Neuropathological hallmarks AD include neurofibrillary tangles composed hyperphosphorylated tau, senile plaques derived from deposition amyloid-β (Aβ) peptides, brain atrophy induced by neuronal loss, synaptic dysfunctions. Death-associated protein kinase 1 (DAPK1) ubiquitously expressed central nervous system. Dysregulation DAPK1 has been shown to contribute various neurological diseases including AD, ischemic stroke Parkinson's (PD). We have established an upstream effect on Aβ tau pathologies apoptosis through kinase-mediated phosphorylation, supporting causal role pathophysiology AD. In this review, we summarize current knowledge about how involved pathological changes hyperphosphorylation, deposition, cell death degeneration. The underlying molecular mechanisms dysregulation are discussed. also review recent progress regarding development novel modulators their potential applications intervention. These findings substantiate as therapeutic target for multifunctional disease-modifying treatments other disorders.

Language: Английский

Citations

12
Illuminating function of the understudied druggable kinome DOI
Shawn M. Gomez, Alison D. Axtman, Timothy M. Willson

et al.

Drug Discovery Today, Journal Year: 2024, Volume and Issue: 29(3), P. 103881 - 103881

Published: Jan. 11, 2024

Language: Английский

Citations

5
Structurally diverse terpenoids and their DRAK2 inhibitory activities: A follow-up study on the vulnerable conifer Pseudotsuga forrestii DOI

Peng‐Jun Zhou,

Ting Huang, Guang‐Lei Ma

et al.

Journal of Molecular Structure, Journal Year: 2024, Volume and Issue: 1305, P. 137754 - 137754

Published: Feb. 8, 2024

Language: Английский

Citations

4
Application of a macrocyclization strategy in kinase inhibitor development DOI Creative Commons
Kun Xing, Shujun Li, Jing Li

et al.

Acta Materia Medica, Journal Year: 2025, Volume and Issue: 4(1)

Published: Jan. 1, 2025

Kinases have a pivotal role in phosphorylation and kinase dysregulation has been implicated the occurrence progression of various diseases. By mid-2024 Food Drug Administration had approved 81 small-molecule inhibitors targeting greater than 30 kinases, providing substantial clinical benefits for patients with cancer other However, many reported exhibit poor target selectivity, limited solubility, issues drug resistance. To address these challenges medicinal chemists used macrocyclization strategy to optimize molecules three macrocyclic (lorlatinib [ALK/ROS1], pacritinib [Flt3/JAK2], repotrectinib [TRK/ROS1]) received FDA approval. The is now widely enhance inhibitory activity, overcome resistance caused by point mutations, improve drug-like properties. In this review we provide comprehensive overview utilization optimization detailing structural modification process from lead compounds that applied recent years. addition, discuss limitations existing propose key considerations development improved molecules. We aim offer valuable insights future advances inhibitor development.

Language: Английский

Citations

0
Comprehensive exploration of programmed cell death landscape in lung adenocarcinoma combining multi-omic analysis and experimental verification DOI Creative Commons
Peng Yu,

Leyang Xiao,

Kaibo Hu

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: Feb. 13, 2025

The mortality and therapeutic failure in lung adenocarcinoma (LUAD) are mainly resulted from the wide metastasis chemotherapy resistance. Up to now, accurate stable predictive prognostic indicator for revealing progress novel strategies of LUAD is infrequent, nonetheless. Diversified programmed cell death (PCD) has been widely confirmed that participated occurrence development various malignant tumors, respectively. In this research, we integrated fourteen types PCD, bulk multi-omic data TCGA-LUAD other cohorts gene expression omnibus (GEO) clinical patients develop our analysis. Consequently, pivotal PCD genes, especially CAMP, CDK5R1, CTSW, DAPK2, GAB2, GAPDH, GATA2, HGF, MAPT, NAPSA, NUPR1, PIK3CG, PLA2G3, SLC7A11, were utilized establish signature, namely index (CDI). validation several external indicated CDI can be regarded as a potential risk factor patients. Combined with common information, nomogram ability was constructed. Besides, according tumor microenvironment (TME) sensitivity some chemotherapeutic drugs further deeply explored. Notably, verification functional experiments demonstrated remarkable correlation between unfold protein response. Given all above, signature predict prognosis exploit precision

Language: Английский

Citations

0
Clinical value assessment for serum hsa_tsr013526 in the diagnosis of gastric carcinoma DOI
Jing Xu, Yue Wang, Xian Li

et al.

Environmental Toxicology, Journal Year: 2024, Volume and Issue: 39(5), P. 2753 - 2767

Published: Jan. 22, 2024

Abstract Gastric carcinoma (GC) is a malignant tumor that detrimental to human health. Transfer RNA‐derived small RNAs are newly identified class of noncoding with specific biological functions aberrantly expressed in cancer. The aim this study was investigate the potential hsa_tsr013526 as biomarker for GC. Quantitative real‐time fluorescence polymerase chain reaction used detect expression level hsa_tsr013526. molecular characteristics were verified by agarose gel electrophoresis, Sanger sequencing, and separation nuclear cytoplasmic RNA fractions. By testing receiver operating characteristic (ROC) curves, diagnostic efficiency GC using determined. Finally, we predicted downstream functional assays bioinformatics analysis. Serum higher patients than healthy donors. showed differential changes patients, gastritis Chi‐squared tests high significantly correlated T stage, lymphatic metastasis, node metastasis stage. ROC curve analysis indicated could be discriminated from donors or based on their serum levels Furthermore, reduced postoperative ( p = .0016). High promotes gastric cancer cell proliferation, invasion, migration. stable specific, dynamic monitoring patients. Therefore, may new diagnosis

Language: Английский

Citations

1
Protection of blood-brain barrier by endothelial DAPK1 deletion after stroke DOI

Zhijiang Gu,

Shaoxun Li,

Jiashang Liu

et al.

Biochemical and Biophysical Research Communications, Journal Year: 2024, Volume and Issue: 724, P. 150216 - 150216

Published: June 4, 2024

Language: Английский

Citations

1
Development of 5-hydroxybenzothiophene derivatives as multi-kinase inhibitors with potential anti-cancer activity DOI

Yara A Abd El-Rahman,

Po‐Jen Chen, Ahmed K. ElHady

et al.

Future Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 16(12), P. 1239 - 1254

Published: May 22, 2024

Chemoresistance in cancer challenges the classical therapeutic strategy of 'one molecule-one target'. To combat this, multi-target therapies that inhibit various cancer-relevant targets simultaneously are proposed.

Language: Английский

Citations

1
ZIPK collaborates with STAT5A in p53-mediated ROS accumulation in hyperglycemia-induced vascular injury DOI Creative Commons

Qichao Wu,

Tingting Xie,

Chang Fu

et al.

Acta Biochimica et Biophysica Sinica, Journal Year: 2024, Volume and Issue: unknown

Published: July 1, 2024

In this study we investigate the role of Zipper-interacting protein kinase (ZIPK) in high glucose-induced vascular injury, focusing on its interaction with STAT5A and effects p53 inducible nitric oxide synthase (NOS2) expression. Human umbilical vein endothelial cells (HUVECs) are cultured under normal (5 mM) (25 glucose conditions. Protein gene expression levels assessed by western blot analysis qPCR respectively, while ROS measured via flow cytometry. ZIPK is manipulated using overexpression plasmids, siRNAs, shRNAs. The inhibitor TC-DAPK6 evaluated a diabetic rat model. Our results show that significantly upregulates ZIPK, STAT5A, p53, NOS2 expressions HUVECs, thus increasing oxidative stress. Silencing STAT5A reduces reactive oxygen species (ROS) accumulation. essential for accumulation, silencing ZIPK reverses these effects. Overexpression combined attenuates alterations expression, thereby preventing cell damage. Coimmunoprecipitation reveals direct between nucleus high-glucose condition. In rats, treatment decreases expressions. findings suggest plays critical injury STAT5A-mediated pathways, proposing potential therapeutic target complications.

Language: Английский

Citations

1
Discovery and Optimization of Isoliquiritigenin as a Death-Associated Protein Kinase 1 Inhibitor DOI
Takeshi Yokoyama,

Kotono Hisatomi,

Saki Oshima

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 279, P. 116836 - 116836

Published: Sept. 4, 2024

Language: Английский

Citations

1