When I was a post-doc in the Katzenellenbogen lab at the University of Illinois Urbana-Champaign, I worked on a number of different projects. I thank Dr. K for allowing me to be contribute to such a variety of research ideas. In addition, I thank him for encouraging me to take control of the projects and to organize collaborators and data. It helped prepare me immensely for running my own lab at University of Richmond.
One of the projects I worked on was such an interesting one (I’m sure I’d describe all of them as interesting… but I’m thinking about this one now). A researcher from St. Jude Children’s Hospital approached us after identifying MPP as an inhibitor of toll-like receptor signaling from a large library screen. MPP was developed by the K-group as a selective estrogen receptor alpha antagonist in the early 2000’s. Actually the K-group has developed a number of estrogen receptor ligands (agonists, antagonists, sub-type selective, tissue selective, etc.) for a variety of medicinal applications (breast cancer, inflammation, obesity, endometriosis, imaging, etc.). So there is quite a bit of knowledge in the group (and within the mind of John Katzenellenbogen) on how to develop a good ER modulator. This project with Hans Haecker at St. Jude was quite different, however; our goal was to remove ER activity while retaining inhibition of toll-like receptor signaling. It was challenging but productive. In the past week, we’ve had two manuscripts published on this work. The first in Science Signaling focuses on the biological impacts of these pyrazole compounds, and the second in ChemMedChem shows the expansive medicinal chemistry it took to optimize the structure-activity relationships.
It is wonderful to see these stories come together during my time at UIUC and UR and for the work to be in print. Enjoy!