Discovery of novel 2,4-diarylaminopyrimidine hydrazone derivatives as potent anti-thyroid cancer agents capable of inhibiting FAK DOI Creative Commons
Hongting Li,

Mei-Qi Jia,

Zhao-Long Qin

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 39(1)

Published: Nov. 19, 2024

In this work, thirty 2,4-diarylaminopyrimidine-based hydrazones were designed, synthesised, and their anti-thyroid cancer activity explored. The majority of compounds exhibit moderate to excellent cytotoxic against FAK overexpressing TPC-1 cells, with IC50 values ranging from 0.113 1.460 μM. Among them, compound 14f displayed exceptional anti-proliferative effect cells (IC50 = μM) potent inhibitory potency 35 nM). silico studies indicated that could well bind (Focal Adhesion Kinase) have favourable pharmacokinetic profiles. addition, inhibit the phosphorylation at Tyr397, Tyr576/577 Tyr925, did not affect expression level in cells. Compound was also effective inhibiting proliferation migration thyroid TPC-1. Thus, these novel 4-arylaminopyrimidine hydrazone derivatives exhibited activities through inhibition FAK.

Language: Английский

Targeting Focal adhesion kinase (FAK) in cancer therapy: A recent update on inhibitors and PROTAC degraders DOI
Xiao Wang, Na Li, Yunhe Liu

et al.

European Journal of Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 276, P. 116678 - 116678

Published: July 14, 2024

Language: Английский

Citations

12
A stumbling block in pancreatic cancer treatment: drug resistance signaling networks DOI Creative Commons
Jinming Liu, Biao Zhang,

Bingqian Huang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 12

Published: Jan. 13, 2025

The primary node molecules in the cell signaling network cancer tissues are maladjusted and mutated comparison to normal tissues, which promotes occurrence progression of cancer. Pancreatic (PC) is a highly fatal with increasing incidence low five-year survival rates. Currently, there several therapies that target networks PC. However, PC "cold tumor" unique immunosuppressive tumor microenvironment (poor effector T infiltration, antigen specificity), targeting single gene or pathway basically ineffective clinical practice. Targeted matrix therapy, targeted metabolic mutant vaccines, other emerging have shown great therapeutic potential, but results been disappointing. Therefore, we summarize identified potential drug-resistant aimed at overcoming barriers existing therapies.

Language: Английский

Citations

1
Metabolite Changes Associated with Resectable Pancreatic Ductal Adenocarcinoma DOI Open Access
Declan McDonnell, Paul R. Afolabi, Umar Niazi

et al.

Cancers, Journal Year: 2025, Volume and Issue: 17(7), P. 1150 - 1150

Published: March 29, 2025

Pancreatic ductal adenocarcinoma (PDAC) is insidious, with only 15-20% of those diagnosed suitable for surgical resection as it either too advanced and has invaded local structures or already spread to distant sites. The associated tumor microenvironment provides a protective shield which limits the efficacy chemotherapeutic agents, but also impairs delivery nutrients required PDAC cells. To compensate this, metabolic adaptions occur provide alternative sources fuel. aim this study explore metabolomic differences between participants resectable compared healthy volunteers (HV). objectives were use nuclear magnetic resonance (NMR) spectroscopy mass spectrometry (MS) determine if induces sufficient adaptations variations could be used discriminate two groups. Plasma samples collected from fasted individuals (n = 23, median age 68 [IQR 56-75], 69.6% male) HV 24, 63 58-71], 54.2% male). Samples analyzed using NMR Biocrates MxP Quant 500 kit at University Hospital Southampton. identified six independent metabolites that significantly discriminated groups, including elevated plasma concentrations 3-hydroxybutyrate citrate, decreased amounts glutamine histidine. MS analysis 84 significant difference cohorts. fold change (FC) > 1.5 in population conjugated bile acids (taurocholic acid, glycocholic glycochenodexoycholic acid). In conclusion, metabolomics, biochemical detected. These indicate plasticity utilization fuel sources.

Language: Английский

Citations

0
Targeting a key FAK-tor: the therapeutic potential of combining focal adhesion kinase (FAK) inhibitors and chemotherapy for chemoresistant non-small cell lung cancer DOI

Emma Geijerman,

Francesca Terrana,

Godefridus J. Peters

et al.

Expert Opinion on Investigational Drugs, Journal Year: 2024, Volume and Issue: 33(11), P. 1103 - 1118

Published: Oct. 22, 2024

NSCLC is the leading cause of cancer-related deaths globally, with a low survival rate primarily due to frequently becoming chemoresistant. Focal adhesion kinase (FAK) non-receptor tyrosine involved in pathways regulating multiple processes cell, including survival, migration, and TME, that contribute both tumor progression drug resistance. Recently, FAK inhibitors (FAKi) have shown promising potential for treatment NSCLC.

Language: Английский

Citations

2
Discovery of novel 2,4-diarylaminopyrimidine hydrazone derivatives as potent anti-thyroid cancer agents capable of inhibiting FAK DOI Creative Commons
Hongting Li,

Mei-Qi Jia,

Zhao-Long Qin

et al.

Journal of Enzyme Inhibition and Medicinal Chemistry, Journal Year: 2024, Volume and Issue: 39(1)

Published: Nov. 19, 2024

In this work, thirty 2,4-diarylaminopyrimidine-based hydrazones were designed, synthesised, and their anti-thyroid cancer activity explored. The majority of compounds exhibit moderate to excellent cytotoxic against FAK overexpressing TPC-1 cells, with IC50 values ranging from 0.113 1.460 μM. Among them, compound 14f displayed exceptional anti-proliferative effect cells (IC50 = μM) potent inhibitory potency 35 nM). silico studies indicated that could well bind (Focal Adhesion Kinase) have favourable pharmacokinetic profiles. addition, inhibit the phosphorylation at Tyr397, Tyr576/577 Tyr925, did not affect expression level in cells. Compound was also effective inhibiting proliferation migration thyroid TPC-1. Thus, these novel 4-arylaminopyrimidine hydrazone derivatives exhibited activities through inhibition FAK.

Language: Английский

Citations

1