Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC
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: The bone marrow of mice with normal ether lipid production (top) contains more white blood cells than are found in the bone marrow of mice with ether lipid deficiency (bottom) (Photo courtesy of Washington University School of Medicine).

Inactivating Fatty Acid Synthase Reduces Inflammation by Interfering with Neutrophil Membrane Function

The enzyme fatty acid synthase (FAS) was shown to regulate inflammation by sustaining neutrophil viability through modulation of membrane phospholipid composition. Neutrophils are the most abundant... Read more

Biochemistry

view channel

Blocking Enzyme Switch Turns Off Tumor Growth in T-Cell Acute Lymphoblastic Leukemia

Researchers recently reported that blocking the action of an enzyme “switch” needed to activate tumor growth is emerging as a practical strategy for treating T-cell acute lymphoblastic leukemia. An estimated 25% of the 500 US adolescents and young adults diagnosed yearly with this aggressive disease fail to respond to... Read more

Therapeutics

view channel
Image: Cancer cells infected with tumor-targeted oncolytic virus (red). Green indicates alpha-tubulin, a cell skeleton protein. Blue is DNA in the cancer cell nuclei (Photo courtesy of Dr. Rathi Gangeswaran, Bart’s Cancer Institute).

Innovative “Viro-Immunotherapy” Designed to Kill Breast Cancer Cells

A leading scientist has devised a new treatment that employs viruses to kill breast cancer cells. The research could lead to a promising “viro-immunotherapy” for patients with triple-negative breast cancer,... Read more

Lab Technologies

view channel
Image: MIT researchers have designed a microfluidic device that allows them to precisely trap pairs of cells (one red, one green) and observe how they interact over time (Photo courtesy of Burak Dura, MIT).

New Device Designed to See Communication between Immune Cells

The immune system is a complicated network of many different cells working together to defend against invaders. Effectively combating an infection depends on the interactions between these cells.... Read more

Business

view channel

Biotech Acquisition Designed to Accelerate the Development and Marketing of Immunosequencing Applications

Adaptive Biotechnologies Corp. (Seattle, WA, USA), a developer of next-generation sequencing (NGS) to profile T-cell and B-cell receptors, has acquired of Sequenta, Inc. (South San Francisco, CA, USA), which is expected to expedite and expand the use of innovative immunosequencing technology for researchers and clinicians... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.