Shaomeng Wang, PhD
Ann Arbor, Michigan
Warner-Lambert/Parke-Davis Professor in Medicine
Professor of Medicine, Pharmacology and Medicinal Chemistry
Co-Director, Molecular Therapeutics Program
Director, Cancer Drug Discovery Program
University of Michigan Comprehensive Cancer Center
Developing new therapies for breast cancer.
In the last few years, a new technology, known as proteolysis targeting chimeric (PROTAC), gained momentum as a novel therapeutic approach. Most drugs do not destroy their targets, they usually only block their activity, but PROTACs eliminate their target protein—making them highly potent. They do so as a function of their design; PROTACs are molecules that have two parts: one attaches to a protein of interest, and the other recruits naturally occurring cellular machinery that degrades proteins. To date, several PROTACs are in clinical development, and Dr Wang and his team are leaders in the discovery and study of PROTAC protein degraders. They are currently developing PROTACs for two therapeutic targets in breast cancer.
Their first target, BRD4, is a key protein for cancer cell survival. After evaluating several candidate versions of PROTAC compounds, Dr. Wang’s team found several that are highly potent and selective for BRD4. They are in the process of performing the pre-clinical studies required before a drug can move into a clinical trial, with the hope of eventually using this PROTAC in triple-negative breast cancers.
The second PROTAC in development by Dr. Wang’s team targets the androgen receptor (AR), which may play an important role in AR-positive, estrogen receptor-negative breast cancers. The team previously developed AR-targeting PROTACs, but those molecules were not suitable for generating a drug that can be taken orally—which is more convenient for patients than receiving drugs intravenously. In the coming year, they will perform laboratory testing of new, orally active formulations of their AR-targeting PROTAC, to see how well they function in breast cancer cells.
Dr. Shaomeng Wang's primary research interest is the discovery and development of novel small-molecule therapeutics for the treatment of human breast cancer and other types of cancer focusing on targeting apoptosis and epigenetics pathways. Dr. Wang has built a comprehensive drug discovery program at the University of Michigan and has advanced four novel anticancer drugs into clinical development and several additional compounds into IND-enabling studies. Dr. Wang has published over 250 manuscripts and is an inventor of more than 50 patents and patent applications.
Dr. Wang's research program consists of three research laboratories. The computational/informatics laboratory has the expertise in lead identification and lead optimization using structure-based methods and informatics. The chemistry laboratory has the capability of synthesizing complex small molecule ligands. The biology/biochemistry/pharmacology laboratory has the capability and expertise for assay development, in-depth molecular mechanism studies and evaluations of the biological activity of new compounds in relevant biochemical assays and laboratory models of human cancer, as well as in vivo pharmacokinetics and pharmacodynamic analysis of these compounds.
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