A small molecule FAK kinase inhibitor, GSK2256098, inhibits growth and survival of pancreatic ductal adenocarcinoma cells.

Focal adhesion kinase (FAK) hyperactivation is common in pancreatic ductal adenocarcinoma (PDAC). A small molecule, GSK2256098 (GlaxoSmithKline), has been developed to inhibit FAK activity through targeting the phosphorylation site of FAK, tyrosine (Y) 397. We sought to determine whether GSK2256098 inhibition of FAK Y397 phosphorylation attenuates PDAC-associated cell proliferation, motility and survival.

The FAK scaffold inhibitor C4 disrupts FAK-VEGFR-3 signaling and inhibits pancreatic cancer growth.

Even with successful surgical resection and perioperative chemotherapy and radiation, pancreatic ductal adenocarcinoma (PDA) has a high incidence of recurrence. Tumor cell survival depends on activation of signaling pathways that suppress the apoptotic stimuli of invasion and metastasis. Focal adhesion kinase (FAK) is a critical signaling molecule that has been implicated in tumor cell survival, invasion and metastasis.

Inhibiting the interaction of cMET and IGF-1R with FAK effectively reduces growth of pancreatic cancer cells in vitro and in vivo.

Pancreatic cancer is one of the most lethal diseases with no effective treatment. Previously, we have shown that FAK is overexpressed in pancreatic cancer and plays a key role in cancer cell survival and proliferation. FAK has been shown to interact with growth factor receptors including cMET and IGF-1R.

A novel small molecule inhibitor of FAK and IGF-1R protein interactions decreases growth of human esophageal carcinoma.

Introduction: Esophageal cancer remains an aggressive disease with poor survival rates. FAK and IGF-1R are two important tyrosine kinases important for cell survival signaling and found to be upregulated in esophageal cancer. Our hypothesis is that a novel small molecule compound that disrupts FAK and IGF-1R protein-protein interactions (PPIs) would decrease the growth of human esophageal cancer.

Rapid determination of banned Sudan I in foodstuffs using a mesoporous SiO2 modified electrode.

Rapid determination of Sudan I in foodstuffs is very important because it was found to be a carcinogen and its use in the food industry was banned. A rapid, sensitive, and convenient electrochemical method was developed for the determination of Sudan I based on the distinctive properties of mesoporous SiO2. The electrochemical responses of Sudan I were investigated.

Small molecule chloropyramine hydrochloride (C4) targets the binding site of focal adhesion kinase and vascular endothelial growth factor receptor 3 and suppresses breast cancer growth in vivo.

FAK is a tyrosine kinase that functions as a key orchestrator of signals leading to invasion and metastasis. Since FAK interacts directly with a number of critical proteins involved in survival signaling in tumor cells, we hypothesized that targeting a key protein-protein interface with druglike small molecules was a feasible strategy for inhibiting tumor growth. In this study, we targeted the protein-protein interface between FAK and VEGFR-3 and identified compound C4 (chloropyramine hydrochloride) as a drug capable of (1) inhibiting the biochemical function of VEGFR-3 and FAK, (2) inhibiting proliferation of a diverse set of cancer cell types in vitro, and (3) reducing tumor growth in vivo.

Vascular endothelial growth factor receptor-3 promotes breast cancer cell proliferation, motility and survival in vitro and tumor formation in vivo.

Vascular endothelial growth factor receptor-3 is a receptor tyrosine kinase that is overexpressed in some human carcinomas, but its role in tumorigenesis has not been fully elucidated. We examined VEGFR-3 expression in normal, nonneoplastic and early stage malignant breast tissues and have shown that VEGFR-3 upregulation in breast cancer preceded tumor cell invasion, suggesting that VEGFR-3 may function as a survival signal. We characterized the biological effects of VEGFR-3 over-expression in human breast cancer cells based on two approaches: gain of function by overexpressing VEGFR-3 in MCF-7 breast cancer cells and loss of function by RNAi-mediated silencing of VEGFR-3 in MCF-7-VEGFR-3 and BT474 cells.