Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
GLOBETECH PUBLISHING
PZ HTL SA

Small Molecule TWEAK-Fn14 Inhibitors Block Cancer Growth

By BiotechDaily International staff writers
Posted on 21 Nov 2013
Image: Immunohistochemistry of TWEAK in human brain tissue (Photo courtesy of Sigma-Aldrich Inc.).
Image: Immunohistochemistry of TWEAK in human brain tissue (Photo courtesy of Sigma-Aldrich Inc.).
Drug developers have identified a series of small molecules that block the interaction of the cytokine TWEAK (TNF-related weak inducer of apoptosis) with its receptor Fn14 (fibroblast growth factor-inducible 14), which slows growth of brain, breast, pancreatic, esophageal, lung, and liver cancers.

TWEAK is a cytokine protein that belongs to the tumor necrosis factor (TNF) family and is a ligand for the Fn14/TWEAKR receptor. This cytokine has overlapping signaling functions with TNF, but displays a much wider tissue distribution. TWEAK can induce apoptosis via multiple pathways of cell death in a cell type-specific manner. This cytokine is also found to promote proliferation and migration of endothelial cells, and thus acts as a regulator of angiogenesis. Overexpression of TWEAK-Fn14 activation has been linked to tissue damage and degradation, including autoimmune diseases, as well as the survival, migration, and invasion of cancer cells.

Investigators at the Translational Genomics Research Institute (Phoenix, AZ, USA) used computer-generated protein-protein docking models to design a targeted library of small molecules predicted to disrupt the TWEAK-Fn14 interaction.

Results published in the November 8, 2013, issue of the Journal of Biological Chemistry described a group of 129 small molecules that produced up to 37% inhibition of TWEAK-Fn14 binding. Four molecules were found to be particularly potent; including compound L524-0366, which completely suppressed TWEAK-induced brain cancer-cell migration without any potential cytotoxic effects.

"Our results show that the TWEAK-Fn14 interaction is a viable drug target, and they provide the foundation for further exploration of this system in researching invasive cancers," said co-senior author Dr. Nhan Tran, associate professor of cancer and cell biology at the Translational Genomics Research Institute. "Because of its unique qualities and association with acute injuries, this drug-like molecule not only could benefit cancer patients, but also might be applied to patients with autoimmunity, heart disease like atherosclerosis, and rheumatoid arthritis."

Related Links:

Translational Genomics Research Institute



Channels

Genomics/Proteomics

view channel
Image: The TheraCyte cell encapsulation device (Photo courtesy of TheraCyte, Inc.).

Encapsulated Human-Insulin-Producing Progenitor Cells Cure Diabetes in Mouse Model

A breakthrough system that allows subcutaneous implantation of encapsulated immature pancreatic cells (beta progenitor cells) was shown to produce enough insulin to correct the symptoms of diabetes in a mouse model.... Read more

Biochemistry

view channel

Mitochondrial Cause of Aging Can Be Reversed

Researchers have found a cause of aging in lab animals that can be reversed, possibly providing an avenue for new treatments for age-related diseases including type 2 diabetes, cancer, muscle wasting, and inflammatory diseases. The researchers plan to begin human trials late 2014. The study, which was published December... Read more

Therapeutics

view channel

Cytokine Identified That Causes Mucositis in Cancer Therapy Patients

The action of the cytokine interleukin 1-beta (IL-1beta) has been found to underlie the onset of mucositis, a common, severe side effect of chemotherapy and irradiation of cancer patients. Mucositis occurs as a result of cell death in reaction to chemo- or radiotherapy. The mucosal lining of the mouth becomes thin, may... Read more

Business

view channel

Analytical Sciences Trade Fair Declared a Rousing Success

Organizers of this year's 24th "analytica" biosciences trade fair have reported significant increases in both the number of visitors and exhibitors compared to the 2012 event. The analytica trade fair for laboratory technology, analysis, and biotechnology has been held at the Munich (Germany) Trade Fair Center every... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.