Stephen Fesik

Stephen Fesik
Alma mater	College of the Holy Cross (BA) University of Connecticut (PhD)
Scientific career
Fields	Medicinal chemistry Structural biology
Workplaces	Vanderbilt University
Doctoral advisor	Alexandros Makriyannis

Stephen William Fesik is an American medicinal chemist and structural biologist known for his research on fragment-based lead discovery. He is a triple professor of biochemistry, a professor of pharmacology, a professor of chemistry, and the Orrin H. Ingram II Chair in Cancer Research and the Tadashi Inagami Chair in Biochemistry at Vanderbilt University.

Early life and education

Fesik was raised in Lincoln, Rhode Island. His father was an accountant. He graduated from the College of the Holy Cross in Worcester, Massachusetts, with a Bachelor of Arts in chemistry in 1975. He then earned his Ph.D. in medicinal chemistry from the University of Connecticut in 1981, under biochemist Alexandros Makriyannis. After receiving his doctorate, he completed postdoctoral research in molecular biophysics and biochemistry at the Yale School of Medicine.

Career

Following his postdoctoral training, Fesik joined Abbott Laboratories, where he conducted research in structural biology and drug discovery for more than two decades. During his tenure he became Divisional Vice President of Cancer Research and led oncology drug discovery programs. While at Abbott, he and colleagues developed SAR by NMR, a method for identifying and optimizing small-molecule ligands using NMR spectroscopy.

In 2009, Fesik joined Vanderbilt University as Professor of Biochemistry, Pharmacology, and Chemistry. He was appointed the Orrin H. Ingram II Chair in Cancer Research and established a research program focused on the discovery of therapeutics for cancer and other diseases using structural biology and medicinal chemistry approaches.

Research

Fesik's research has focused on fragment-based drug discovery, structure-based drug design, medicinal chemistry, and the application of NMR spectroscopy to drug discovery. His work has included the development of small-molecule inhibitors targeting protein–protein interactions and proteins involved in cancer biology, including members of the BCL-2 family, MCL-1, KRAS, MYC, and WDR5. He is known for developing the Structure–Activity Relationships by Nuclear Magnetic Resonance (SAR by NMR) methodology, an approach used in fragment-based drug discovery.

SAR by NMR has been described in the scientific literature as one of the methods that established fragment-based drug discovery as a strategy in pharmaceutical research.

Honors and awards

• NIH Director's Pioneer Award (2010).

• AACR Award for Outstanding Achievement in Chemistry in Cancer Research (2012).

• Elected Fellow of the American Association for the Advancement of Science (AAAS).

• SBS Technology Innovation Award.

Selected publications

• Shuker, Steven B.; Hajduk, Philip J.; Meadows, Raymond P.; Fesik, Stephen W. (1996). "Discovering high-affinity ligands for proteins: SAR by NMR". Science. 274 (5292): 1531–1534. doi:10.1126/science.274.5292.1531. PMID 8929414.

• Oltersdorf, Thomas; et al. (2005). "An inhibitor of Bcl-2 family proteins induces regression of solid tumors". Nature. 435 (7042): 677–681. doi:10.1038/nature03579. PMID 15902208.

• Fesik, Stephen W. (2025). "Drugging Challenging Cancer Targets using Fragment-Based Methods". Chemical Reviews. 125 (7): 3586–3594. doi:10.1021/acs.chemrev.4c00987.