Structure-Guided Design of Novel Competitive Aromatase Inhibitor for the Treatment of Endometriosis

Abby R. Held
Dr. Bill R. Miller, Faculty Mentor

Endometriosis is an estrogen dependent disease characterized by endometrial tissue growing in extrauterine sites. Aromatase is an enzyme that produces estrogens, and is abnormally expressed in endometriotic tissue. Aromatase, implicated in hormone-dependent breast cancer, has three inhibitors currently available for public use: exemestane, letrozole, and anastrozole. Little has been done to study how these could be useful in the treatment of endometriosis, however pilot studies have been successful in reducing the pain-free interval between pelvic surgeries. These drugs, however, have been linked to several negative side effects. Isoflavanones are a class of natural products that act as competitive aromatase inhibitors while reducing these side effects. Here, a novel isoflavanone is in development for the purpose of aromatase inhibition using molecular dynamics (MD) simulations. Several promising isoflavanones have been identified, and modifications of these structures are in development to design an inhibitor with a greater binding affinity than exemestane.

Keywords: endometriosis, cancer, drug design, aromatase, computational chemistry, competitive inhibition

Topic(s):Chemistry
Biochemistry and Molecular Biology
Physics

Presentation Type: Oral Presentation

Session: TBA
Location: TBA
Time: TBA