Dr. Amy Hauck Newman’s research focuses on the design and synthesis of novel small molecules to study the structure and function of the dopamine and serotonin transporters and the dopamine D2 receptor family (D2/D3/D4). Compounds with high affinities and selectivities for these specific targets are prepared for characterization at the cellular and molecular level. Structure-activity relationships are built on the affinities and functional efficacies of these molecules and the 3D-structures of the target proteins, based on computational models from crystal structures of the proteins themselves or homologous proteins. In addition, specific tools such as fluorescent, photoactive and/or radiolabeled ligands are synthesized for structure-function studies. The combination of state of the art synthetic organic chemistry with computational modeling has resulted in the discovery of numerous and novel molecular probes, several of which are now commercially available.
Through these efforts, her team has identified a class of novel dopamine uptake inhibitors that are not cocaine-like and determined the mechanistic basis for these behavioral differences. They have created photoaffinity and fluorescent ligands that have allowed the elucidation of drug-transporter interaction and visualization of transporter trafficking at the cellular level. Her laboratory has also elucidated the molecular determinants of selectivity and efficacy at the dopamine D3 receptor, based on the D3 crystal structure and a novel synthon strategy. It is envisioned that this multidisciplinary approach will provide new leads toward the development of potential pharmacotherapeutic agents for the treatment of substance use disorders.
She has published >300 original articles, reviews and invited commentaries in peer reviewed journals and is the inventor on 13 patents, several of which have been licensed by Pharma. In 2016, Dr. Newman was the first woman to receive the Philip Portoghese Lectureship Award, awarded by the Division of Medicinal Chemistry and the Journal of Medicinal Chemistry, American Chemical Society.