Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Novel Drug Interferes with Androgen Receptors and Blocks Prostate Cancer Growth

By BiotechDaily International staff writers
Posted on 14 Jun 2013
Print article
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


Print article

Channels

Genomics/Proteomics

view channel
Image: Healthy blood cells along with sickle-cell diseased cells (Photo courtesy of Science Picture Co./Corbis).

Gene Editing Corrects Hemoglobin Defects in Beta-Thalassemia and Sickle Cell Disease

A team of hematology researchers used the CRISPR/Cas9 gene editing technique to correct the mutations that cause defective blood cell morphology in beta-thalassemia and sickle cell disease.... Read more

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Business

view channel

Collaborative Agreement to Aid in Setting Guidelines for Evaluating Potential Ebola Therapy

Cooperation between an Israeli biopharmaceutical company and medical branches of the US government is designed to set ground rules for continued evaluation of an experimental therapy for Ebola virus disease. RedHill Biopharma Ltd. (Tel Aviv, Israel), a biopharmaceutical company primarily focused on development and c... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.