The Hergenrother Research Group at the University of
Illinois Champaign-Urbana

Professor Paul J. Hergenrother

Paul J. Hergenrother was born in 1972 and raised in Akron, Ohio. He attended the University of Notre Dame, where he received his B.S. in Chemistry in 1994. From there Paul moved to the University of Texas at Austin, to conduct graduate research under the direction of Professor Stephen F. Martin and received his PhD in 1999. He then conducted postdoctoral research at the American Cancer Society at Harvard University, under Professor Stuart L. Schreiber. Paul is currently a Professor and the Kenneth L. Rinehart Jr. Endowed Chair in Natural Products Chemistry at the University of Illinois Champaign-Urbana. He is also the co-founder and chief scientific officer of Vanquish Oncology.

The Hergenrother group is focused on the synthesis of complex organic compounds and their application in anticancer and antibacterial research. Recently, the Hergenrother group identified and prepared Raptinal, a small molecule that inducesapoptotic cell death at unparalleled speed via the intrinsic pathway, a process that typically takes many hours. This impressive and unmatched activity lends Raptinal to many applications in biology, pharmacology, and chemistry.

Raptinal has recently been shown to induce rapid apoptosis via the intrinsic pathway in multiple cell lines, and in whole organisms. Additionally, Raptinal shows tumor growth inhibition in vivo. Apoptosis is a form of programmed cell death characterized by cell membrane blebbing followed by cell disassembly. Raptinal showed an average IC₅₀ of 1.5 ± 0.3 μM across 22 cell lines after 24h of incubation, and was shown to release cytochrome c within minutes. Structural activity relationship assays against 25 small molecules showed Raptinal to be the best performer, with the presence of the aldehyde functionality being essential for the activity. The gene knockdown of known siRNA involved with intrinsic apoptosis pathway in cell lines increased cell survivability after Raptinal treatment, suggesting Raptinal’s mechanism of action with the intrinsic pathway. Further, incubation of cell lines with mitochondrial inhibitors afforded quantitative protection against Raptinal, indicating that mitochondrial function was essential for apoptosis to occur. Further, in whole organisms Raptinal induced cell apoptosis in live zebrafish, and showed tumor inhibition activity in mice while also not exhibiting hematological toxicity.