Dr. Jung-Mo Ahn, associate professor of chemistry at The University of Texas at Dallas, has designed and synthesized a novel small molecule that might become a large weapon in the fight against prostate cancer.
In a study published online May 28 in the journal Nature Communications, Ahn and his colleagues at UT Southwestern Medical Center describe the rational design of the molecule, as well as laboratory tests that show its effectiveness at blocking the cancer-promoting function of proteins called androgen receptors.
Androgen receptors are found inside cells and have complex surfaces with multiple "docking points" where various proteins can bind to the receptor. Each docking point has a unique shape, so only a correctly shaped molecule will fit.
Androgen hormones, such as testosterone, are the primary molecules that bind to androgen receptors. Such binding sets off a chain of events that activates several different processes in the human body, including stimulating the development and maintenance of male characteristics.
Looking for a new approach to battle prostate cancer, Ahn and his colleagues keyed in on blocking a critical docking point on the androgen receptor.
"When a tumor is trying to grow, activation of this location provides what the tumor needs," Ahn said. "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's why we thought our approach might lead to potent efficacy with fewer side effects."
Using computer-assisted molecular modeling, Ahn designed a helix-mimicking small molecule that fits precisely into a pocket on the androgen receptor that is associated with prostate cancer. Collaborating with senior study author Dr. Ganesh Raj, associate professor of urology at UT Southwestern and a specialist in tre
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University of Texas at Dallas