Biochemistry & Cancer Biology

Paul W. Erhardt, Ph.D.

Paul W. Erhardt, Ph.D.
Director, Center for Drug Design & Development
Professor, Medicinal & Biological Chemistry
Joint Professor, Biochemistry and Cancer Biology
paul.erhardt@utoledo.edu 

RESEARCH INTERESTS

As Director of the University of Toledo’s Center for Drug Design and Development (UT’s CD3), I oversee an established core of interdisciplinary investigators who operate as a cohesive team across seven key areas of competency: (i) Computational chemistry and molecular modeling/docking; (ii) Synthetic medicinal chemistry ‘hit-follow-up’ and ‘early-ADMET-optimization’; (iii) Frontline screening and biological testing using biochemical and cell culture assays in 96-well, semi-automated format; (iv) Analytical and bioanalytical chemistry using ‘validated GLP-compliant’ assay methods emphasizing LC-MS/MS instrumentation; (v) Scale-up and process chemistry optimization with an eye toward green chemistry; (vi) Secondary pharmacological and advanced ADMET-PK studies in vitro and in vivo; and, (vii) IP and patent protection strategies. Specializing in the development of small molecule agents, the CD3 can assist in the translation of molecular biology and clinical concepts all the way to an IND submission associated with promising diagnostic and biomarker tools, treatment, or disease prevention paradigms. I have considerable experience in synthetic medicinal chemistry, the latter sometimes requiring development of novel methodology (e.g. refs. a,b), and in the optimization of initial ‘hit’ compounds relative to potency, target selectivity and ADMET properties (e.g. refs. c, d) while working in industry and leading the CD3 at UT. Likewise, I have expertise in drug metabolism including the design of prodrugs and soft drugs, for which I have contributed several invited chapters to highly regarded texts within the fields of medicinal chemistry and pharmacology (exemplary refs. provided below).

(a) Erhardt, P.W. (1979). Curtius conversion of acids to amines under neutral conditions via an anthrylmethyl carbamate. J. Org. Chem., 44, 883.

(b) Malik, N. & Erhardt, P. (2013). Synthesis of 6a-hydroxypterocarpans via intramolecular benzoin condensation. Tet. Lett., 54, 4121-4124.

(c) Shaw, K., Erhardt, P., Hagedorn, A., Pease, C., Ingebretsen, W. & Wiggins, J. (1992). Cardiotonic agents 7. Prodrug derivatives of 4-ethyl-1,3-dihydro-5-[4-(2-methyl)-1H-imidazol-1-yl)benzoyl]-2H-imidazol-2-one. J. Med. Chem., 35, 1267-1272.

(d) Trabbic, C.J., Overmeyer, J.H., Alexander, E.M., Crissman, E.J., Kvale, H.M., Smith, M.A., Erhardt, P.W. & Maltese, W.A. (2015) Synthesis and biological evaluation of indolyl-pyridinyl-propenones having either methuosis or microtubule disruption activity. J. Med. Chem., 58, 2489-2512.

EDUCATION:

B.A. 1969 Chemistry, Univ. of Minnesota, Minneapolis
Ph.D. 1974 Medicinal Chemistry, Univ. of Minnesota, Minneapolis
Postdoc 1974-75 Bioanalytical Chemistry, Univ. of Texas, Austin

EMPLOYMENT/ACADEMIC APPOINTMENTS:

1975-1976 Assistant Professor, Medicinal Chemistry & Pharmacology, Northeastern University, Boston, MA
1976-1983 American Critical Care, McGraw Park, IL
  1976 Research Investigator, Medicinal Chemistry
  1979 Senior Research Investigator, Medicinal Chemistry
  1982 Group Leader, Medicinal Chemistry
1983-1994 Berlex Laboratories, Inc., Cedar Knolls, NJ
  1983 Section Head, Medicinal Chemistry
  1988 Assistant Director, Medicinal Chemistry
  1991 Assistant Director, Drug Discovery & Technology
1994-present The University of Toledo, College of Pharmacy, Toledo, OH
  1994 Director, Center for Drug Design & Development (CD3) and Professor of Medicinal Chemistry
  1997 Interim Assistant Dean, Administrative & Professional Affairs (one year)
  2004 Adjunct Professor, Department of Biology
  2008 Adjunct Professor, Department of Pharmacology
  2009 Joint Professor, Department of Biochemistry & Cancer Biology
  2012 Distinguished University Proessor

PATENTS:

One of the compounds that I designed, synthesized and developed is marketed as Brevibloc® (USAN: Esmolol Hydrochloride).

RECENT PUBLICATIONS:  (co-author/inventor of more than 125 scientific papers/U.S. patents)

Malik, N., Zhang, Z. Erhardt, P. (2015) Total synthesis of (+)-glyceollin II and a dihydro derivative. J. Nat. Prod. 12:2940-2947.

Trabbic, C., Overmeyer, J.H., Alexander, E.M., Crissman E.J., Kvale H.M., Smith, M.A., Erhardt P.W. and Maltese, W.A. (2015) Synthesis and biological evaluation of indolyl-pyridinyl-propenones having either methuosis or microtubule disruption activity. J. Med. Chem. 58:2489-2512.

Trabbic, C., Dietsch, H., Alexander, E., Nagy,, P., Roinson, M., Overmeyer J., Maltese, W. and Erhardt, P. (2014) Differential induction of cytoplasmic vacuolization and methuosis by novel 2-indolyl-substituted pyridinylpropeones.  ACS Med. Chem. Lett., 5:73-77.

Erhardt, P. (2014 & 2015). (I) Drug design and development: A research center more than twenty years in the making; & (ii) Drug design and development: Part II - reflections from an academic-based center. Chemistry International 36 & 37, pgs. (i) cover caption, 8-13,27-28; & (ii) 12-15.

Jetson, R., Malik, N., Luniwal, A., Chari, V., Ratnam, M., and Erhardt, P. (2013) Practical synthesis of a chromene analog for use as a retinoic acid receptor alpha-antagonist lead compound. Eur. J. Med. Chem., 63:104-108.

Nagy, P.I. and Erhardt, P. (2012) On the interaction of aliphatic amines and ammonium ions with carboxylic acids in solution and in receptor pockets. J. Phys. Chem. B 116:5425-5436.

Luniwal, A., Wang, L., Pavlovsky, A., Erhardt, P. and Viola, R. (2012) Molecular docking and enzymatic evaluation to identify selective inhibitors of aspartate semialdehde dehydrogenase. Bioorganic and Medicinal Chem., 20:2950-2956.

Sarver, J.G., Trendel, J.A., Bearss, N.R., Wang, L., Luniwal, A., Erhardt, W.W., and Viola, R.E. (2012) Early stage efficacy and toxicology screening for antibiotics and enzyme inhibitors. J. Biomol. Screen. 17:673-682.

Robinson, M.W., Overmeyer, J.H., Young, A.M., Erhardt, P.W., and Maltese, W.A. (2012) Synthesis and evaluation of indole-based chalcones as inducers of methuosis, a novel type of nonapoptotic cell deathJ. Med. Chem. 55:1940-1956.

Luniwal, A., Khupse, R., Reese, M., Liu, J., El-Dakdouki, M., Malik, N., Fang, L. and Erhardt, P. (2011) Multigram Synthesis of glyceollin I. Org. Process Res. Dev., 15:1149-1162.

Khupse, R., Sarver, J., Trendel, J., Bearss, N., Reese, M., Wiese, T., Boue, S., Burrow, M., Cleveland, T., Bhatnagar, D. and Erhardt, P. (2011) Biomimetic synthesis and antiproliferative properties of racemic, natural (-) and unnatural (+) glyceollin I. J. Med. Chem., 54:3506-3523.

El-Dakdouki,, M.H., Adamsi, N., Foster, L. Hacker, M.P., and Erhardt, P.W. (2011) Hypoxia activated prodrugs of a 9-aza-anthrapyrazole derivative that has promising anticancer activity. J. Med. Chem. 54:8224-8227.

Shan, Y.Y., Zhang, C.M., Tang, L.Q., Liu, Z.P. Bearss, N.R., Sarver, J.G., Luniwal, A. and Erhardt, P.W. (2011) Syntheses of 2,3-diarylated 2H-benzo[e][1,2]thiazine 1,1-dioxides and their 3,4-dihydro derivatives, and assessment of their inhibitory activity against MCF-7 breast cancer cells. Med. Chem. 7:561-571.







Last Updated: 4/8/16