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

Novel Drug Interferes with Androgen Receptors and Blocks Prostate Cancer Growth

By BiotechDaily International staff writers
Posted on 14 Jun 2013
Image: Contributing author Dr. Jung-Mo Ahn (Photo courtesy of the University of Texas at Dallas).
Image: Contributing author Dr. Jung-Mo Ahn (Photo courtesy of the University of Texas at Dallas).
A novel, small molecule peptidomimetic drug called D2 interferes with the function of androgen receptors, blocking the androgen-induced proliferation of prostate cancer cells in vitro and inhibiting tumor growth in a mouse xenograft model.

A peptidomimetic is a small protein-like chain designed to mimic a peptide. These molecules typically arise either from modification of an existing peptide, or by designing similar molecules that mimic peptides, such as peptoids and beta-peptides. The altered chemical structure is designed to advantageously adjust molecular properties such as stability or biological activity. These modifications involve changes to the peptide that will not occur naturally (such as altered backbones or the incorporation of non-natural amino acids).

Investigators at the University of Texas (Dallas, USA) and colleagues at the University of Texas Southwestern Medical Center (Dallas, USA) used computer-assisted molecular modeling techniques to design a helix-mimicking small molecule that could bind selectively to a pocket on the androgen receptor associated with prostate cancer.

They reported in the May 28, 2013, online edition of the journal Nature Communications that this molecule, D2, blocked androgen-induced nuclear uptake and genomic activity of the androgen receptor. Furthermore, D2 abrogated androgen-induced proliferation of prostate cancer cells in vitro, and inhibited tumor growth in a mouse xenograft model. D2 also disrupted androgen receptor–coregulator interactions in ex vivo cultures of primary human prostate tumors. D2 was found to be stable, nontoxic, and efficiently taken up by prostate cancer cells.

"When a tumor is trying to grow, activation of this location provides what the tumor needs," said contributing author Dr. Jung-Mo Ahn, associate professor of chemistry at the University of Texas. "There are other surfaces on the androgen receptor that are free to continue working with their respective proteins and to continue functioning. We sought to block only one set of interactions that contribute to prostate cancer growth. That is why we thought our approach might lead to potent efficacy with fewer side effects."

"We have shown that our molecule binds very tightly, targeting the androgen receptor with very high affinity," said Dr. Ahn. "We also have confirmed that it inhibits androgen function in these cells, which is a promising finding for drug development. We showed that it does work through these mechanisms, and it is as effective in inhibiting the proliferation of prostate cancer cells as other compounds currently in clinical trials."


Related Links:

University of Texas

University of Texas Southwestern Medical Center


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.