May 28, 2014
Dr. Hollis Showalter, Research Professor and Co-Director of the Vahlteich Medicinal Chemistry Core

Hollis Showalter, PhD, Research Professor and Co-Director of the Vahlteich Medicinal Chemistry Core, presented two invited lectures at national conferences this spring. 

The first, entitled “Studies directed toward the design of benzoxazinorifamycins less susceptible to emerging resistance,” was part of a American Chemical Society National Meeting Symposium on new areas of tuberculosis (TB) research.

  • The benzoxazinorifamycins are derivatives of rifampin, which is a first-line drug to treat TB. However, serious multi-drug resistance has developed to this and other currently used drugs. In a collaboration with Penn State, U-M medicinal chemists have synthesized novel benzoxazinorifamycins that show potential for lowered susceptibility to this resistance. 

The second, entitled “Deubiquitinases. The new kinases in human medicine,” was given at the National Medicinal Chemistry Symposium.

  • This topic outlined research being carried out in a collaboration with the U-M Cancer Center. Under normal processes, there are various regulatory mechanisms to eliminate damaged cells from the body.  However, under abnormal circumstances, a relatively new class of enzymes called “deubiquitinases” can become too active resulting in the emergence of various types of cancer including myelomas, lymphomas, and melanoma. Dr. Showalter and Med Chem colleagues have developed a novel class of inhibitors that specifically inhibit deubiquitinases and show excellent activity in shrinking tumors in mice transplanted with these cancers. Additional studies are ongoing with an advanced compound, which might have potential for clinical studies.  

Medicinal Chemistry Department collaborators are Irosha Nawarathne, Nathan Scharf, Paul Kirchhoff, Yafei Jin, and George Garcia.