Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC

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: An adult cardiomyocyte has re-entered the cell cycle after expression of miR302-367 (Photo courtesy of the laboratory of Dr. Edward Morrisey, University of Pennsylvania).

Certain MicroRNAs Stimulate Regeneration of Adult Heart Tissue

Cardiac disease researchers working with a mouse model have discovered that by inducing a subset of microRNAs (miRNAs) that are active during development but silenced in the adult they could cause damaged... Read more

Biochemistry

view channel
Image:  Model depiction of a novel cellular mechanism by which regulation of cryptochromes Cry1 and Cry2 enables coordination of a protective transcriptional response to DNA damage caused by genotoxic stress (Photo courtesy of the journal eLife, March 2015, Papp SJ, Huber AL, et al.).

Two Proteins Critical for Circadian Cycles Protect Cells from Mutations

Scientists have discovered that two proteins critical for maintaining healthy day-night cycles also have an unexpected role in DNA repair and protecting cells against genetic mutations that could lead... Read more

Business

view channel

“Softer” Mass Spec Techniques Gain Advantage in Biomarker Discovery

Two mass spectrometry (MS) technologies, MALDI and DESI, are increasing in applications as their effectiveness is established, according to Kalorama Information (New York, NY, USA) in its report “Proteomics Markets for Research and IVD Applications (Mass Spectrometry, Chromatography, Microarrays, Electrophoresis, Immunoassays,... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.