Summary

Hollis Showalter joined the University of Michigan in 2006 after more than 25 years of drug discovery and development experience within the pharmaceutical industry.  He has broad experience in synthetic medicinal chemistry and has led a number of campaigns resulting in agents proceeding to clinical trials.  One of these, Nipent™, is marketed for the treatment of hairy cell leukemia.  He was the founding Director of the University of Michigan Vahlteich Medicinal Chemistry Core (UMVMCC.org), which works with collaborators to advance their drug discovery efforts by selecting appropriate leads from high-throughput screening (HTS) campaigns, contributing synthetic and medicinal chemistry strategies to grant proposals, and developing biological probes or potential therapeutic agents for biological investigation.  He also provides expertise on intellectual property protection.  He has published 159 peer reviewed manuscripts/reviews/book chapters, and 154 meeting abstracts.  He holds 44 issued or applied for United States patents.

He has served professionally on numerous internal and external committees, including industry, UM, and the American Chemical Society Medicinal Chemistry Division.  Showalter is currently involved in a number of internal and external research collaborations and assists in the teaching of Medicinal Chemistry PhD students.

For a complete listing of Showalter’s professional history, refer to his CV.

Research Interests

  • Natural products modification and heterocyclic chemistry synthesis

  • Designing in physicochemical properties to high-throughput screen hits that confer “druggability” (e.g., conformity to Lipinski rules, absence of toxicophores)

  • Development of structure-activity relationships (SAR) to derive compounds with optimal pharmacokinetic and metabolic profiles toward the initiation of in vivo studies

  • Principal therapeutic focus in infectious diseases and oncology with extensive knowledge of associated targets, especially deubiquitinases, RNA polymerase, and protein kinases

Selected Publications

  • Madak JT, Cuthbertson CR, Chen W, Showalter HD, Neamati N.  Design, Synthesis, and Characterization of Brequinar Conjugates as Probes to Study DHODH Inhibition.  Chemistry - A European Journal, http://dx.doi.org/10.1002/chem.201702999.  PMID: 28833638

  • Jin Y, Huang X, Papke RL, Jutkiewicz E, Showalter HD, Zhan C-G.  Design, Synthesis, and Biological Activity of 5′-Phenyl-1,2,5,6-tetrahydro-3,3'-bipyridine Analogues as Potential Antagonists of Nicotinic Acetylcholine.  Bioorg. Med. Chem. Lett., 2017, 27:4350-4353.  PMID: 28838693.

  • Carpenter C, Sorenson RJ, Jin Y, Klossowski S, Cierpicki T, Gnegy M, Showalter HD.  Design and Synthesis of Triarylacrylonitrile Analogues of Tamoxifen with Improved Binding Selectivity to Protein Kinase C. Bioorganic & Medicinal Chemistry, 2016, 24:5495-5504.  PMID: 27647375.

  • Xu H, Majmudar JD, Davda D, Ghanakota P, Kim KH, Carlson HA, Showalter HD, Martin BR, Amidon GL.  Substrate-competitive Activity-based Profiling of Ester Prodrug Activating Enzymes. Molecular Pharmaceutics, 2015, 12:3399-3407. PMID: 26262434.

  • Peterson LF, Sun H, Liu Y, Potu H, Kandarpa M, Ermann M, Courtney SM, Young MA, Showalter HD, Sun D, Jakubowiak AJ, Malek SN, Talpaz M, Donato NJ.  Targeting Deubiquitinase Activity with a Novel Small Molecule Inhibitor as Therapy for B-cell Malignancies. Blood, 2015,125:3588-3597.  PMID: 25814533.

  • Molodtsov V, Nawarathne IN, Scharf NT, Kirchhoff PD, Showalter HDH, Garcia GA, Murakami KS. X-ray Crystal Structures of the Escherichia coli RNA Polymerase in Complex with Benzoxazinorifamycins.  J. Med. Chem., 2013, 56: 4758-4763.  PMID: 23679862.

  • Lall MS, Hoge G, Tran T, Kissel W, Murphy ST, Taylor C, Hutchings K, Samas B, Ellsworth E, Curran T, Showalter HDH. Stereoselective Synthesis of (S)-3-(Methylamino)-3-((R)-pyrrolidin-3-yl)propanenitrile. J. Org. Chem., 2012, 77: 4732-4739.