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 first 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 153 peer reviewed manuscripts/reviews/book chapters, and 150 meeting abstracts. He holds 43 issued or applied for patents.
He has served professionally on numerous internal and external committees, both in industry and at UM, and is currently a member of the American Chemical Society Medicinal Chemistry Division Awards Committee. Showalter is involved in the teaching and mentoring of Medicinal Chemistry PhD students.
For a complete listing of Showalter’s professional history, refer to his CV.
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
Passalacqua KD, Charbonneau M-E, Donato NJ, Showalter HD, Sun D, Wen B, He M, Sun H, O’Riordan MXD, Wobus CE. Anti-infective Activity of 2-Cyano-3-acrylamide Inhibitors with Improved Drug-like Properties against two Intracellular Pathogens. Antimicrobial Agents and Chemotherapy, 2016, 60:4183-4196. PMID: 27139470.
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.
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, DOI: http://dx.doi.org/10.1182/blood-2014-10-605584.
Charbonneau M-E, Gonzalez-Hernandez MJ, Showalter HD, Donato NJ, Wobus CE, O’Riordan MXD. Small Molecule Deubiquitinase Inhibitors Promote Macrophage Anti-infective Capacity. Plos One, 2014, 9:e104096. PMID: 25093325.
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.
Showalter HDH, Denny WA. A Roadmap for Drug Discovery and its Translation to Small Molecule Agents in Clinical Development for Tuberculosis Treatment. Tuberculosis, 2008; 88: Suppl 1:S3-S17.