Department of Medicinal and Biological Chemistry

Isaac T. Schiefer, Ph.D.

Schiefer

Associate Professor

Director, Center for Drug Design and Development (CD3)
Associate Director, Shimadzu Laboratory for Pharmaceutical Research Excellence

Office: Frederic and Mary Wolfe Center 284C
Lab: Frederic and Mary Wolfe Center 275C
Phone: 419.383.1935
isaac.schiefer@utoledo.edu
Schiefer Lab Website
Biosketch

Education

Bach. Sci. Pharm. Sci.
Medicinal and Biological Chemistry
           2007            The University of Toledo
Ph.D.
Medicinal Chemistry
           2012            Univ. of Illinois at Chicago
Post-doctoral Fellow
Chemical Biology
           2013            Northwestern University

Media

 

Research Interests

Our lab carries out research in two areas at the interface of medicinal chemistry and chemical biology:

1)      small molecule hit-to-lead optimization- using synthetic, bioanalytical, and bioorganic chemistry

2)      target identification using techniques in chemical and cellular biology

We are interested in creating and developing novel therapies for neurodegeneration, with an emphasis on Alzheimer’s disease (AD). Our primary long-term objective is to translate SAFE and EFFECTIVE novel small molecule therapies into the clinic to improve patient outcomes and human health. Our current work involves the development of attenuated nitric oxide (NO) mimetics as novel therapeutic candidates for stroke and AD.

Representative Recent Publications (starting from most recent)

Shi, H.; Fan, X.; Horton, A.; Haller, S. T.; Kennedy, D. J.; Schiefer, I. T.; Dworkin, L.; Cooper, C. J.; Tian, J. The Effect of Electronic-Cigarette Vaping on Cardiac Function and Angiogenesis in Mice. Scientific Reports, 2019, 9:4085. https://www.nature.com/articles/s41598-019-40847-5.pdf

Horton, A.; and Schiefer, I. T. Pharmacokinetics and Pharmacodynamics of Nitric Oxide Mimetic Agents. Nitric Oxide, 2019; 84, 69-78. https://doi.org/10.1016/j.niox.2019.01.001

Obrenovich, M. E.; Schiefer, I. T.; Bongiovanni, R.; Li, L.; Donskey, C. J.; Jaskiw, G. E. Quantification of Phenolic Acid Metabolites in Humans by LC-MS – A Structural and Targeted Metabolomics Approach. Bioanalysis, 2018, 10 (19), 1591-1608. doi: 10.4155/bio-2018-0140.

Horton, A.; Nash, K.; Tackie-Yarboi, E.; Kostrevski, A.; Novak, A.; Raghavan, A.; Tulsulkar, J.; Alhadidi, Q.;  Wamer, N.; Langenderfer, B.; Royster, K.; Ducharme, M.; Hagood, K.; Post, M.; Shah, Z. A.; Schiefer, I. T. Furoxans (Oxadiazole-4N-oxides) with Attenuated Reactivity are Neuroprotective, Cross the Blood Brain Barrier, and Improve Passive Avoidance Memory. Journal of Medicinal Chemistry, 2018; 61(10), 4593-4607. doi: 10.1021/acs.jmedchem.8b00389

Nash, K.M., Schiefer, I. T.*; Shah, Z.S.*, Development of a reactive oxygen species-sensitive nitric oxide synthase inhibitor for the treatment of ischemic stroke. Free Radicals in Biology and Medicine 2018, 115, 395-404. *denotes co-corresponding authors 10.1016/j.freeradbiomed.2017.12.027.

Kurogi K., Yoshihama M., Horton A., Schiefer I.T., Krasowski M.D., Hagey L.R., Williams F.E., Sakakibara Y., Kenmochi N., Suiko M., Liu M.C. Identification and characterization of 5α-cyprinol-sulfating cytosolic sulfotransferases (Sults) in the zebrafish (Danio rerio). Journal of Steroid Biochemistry and Molecular Biology. 2017, 174, 120-127. 10.1016/j.jsbmb.2017.08.005

Alasmari F., Crotty Alexander L.E., Nelson J.A., Schiefer I.T., Breen E., Drummond C.A., Sari Y. Effects of chronic inhalation of electronic cigarettes containing nicotine on glial glutamate transporters and α-7 nicotinic acetylcholine receptor in female CD-1 mice. Progress in Neuropsychopharmacology and Biological Psychiatry. 2017, 77, 1-8. 10.1016/j.pnpbp.2017.03.017

Fà M., Zhang H., Staniszewski A., Saeed F., Shen L.W., Schiefer I.T., Siklos M.I., Tapadar S., Litosh V.A., Libien J., Petukhov P.A., Teich A.F., Thatcher G.R., Arancio O. Novel Selective Calpain 1 Inhibitors as Potential Therapeutics in Alzheimer's Disease.  Journal of Alzheimer's Disease, 2016, 49(3), 707-21. 10.3233/JAD-150618.

Yamamoto A., Kurogi K., Schiefer I.T., Liu M.Y., Sakakibara Y., Suiko M., Liu M.C. Human Cytosolic Sulfotransferase SULT1A3 Mediates the Sulfation of Dextrorphan. Biological and Pharmaceutical Bulletin 2016, 39(9), 1432-1436. 10.1248/bpb.b16-00015.

Trippier, P. C.; Zhao, K. T.; Fox, S.; Schiefer, I. T.; Benmohamed, R.; Moran, J.; Kirsch, D. R.; Morimoto, R. I.; Silverman, R. B. Proteasome Activation is a Mechanism for Pyrazolone Small Molecules Displaying Therapeutic Potential in Amyotrophic Lateral Sclerosis. ACS Chemical Neuroscience 2014, 5 (9), 823-829. 10.1021/cn500147v

Schiefer, I. T.; Tapadar, S.; Litosh, V.; Siklos, M.; Scism, R.; Wijewickrama, G. T.; Chandrasena, E. P.; Sinha, V.; Tavassoli, E.; Brunsteiner, M.; Fa’, M.; Arancio, O.; Petukhov, P.; Thatcher, G. R. J. Design, Synthesis, and Optimization of Novel Epoxide Incorporating Peptidomimetics as Selective Calpain Inhibitors. Journal of Medicinal Chemistry, 2013, 56, 6054–68. 10.1021/jm4006719

Schiefer, I. T.; VandeVrede, L.; Fa', M.; Arancio, O.; Thatcher, G.R.J. Furoxans (1, 2, 5 Oxadiazole-N-Oxides) as Novel NO Mimetic Neuroprotective and Procognitive Agents. Journal of Medicinal Chemistry, 2012, 55, 3076-3087. 10.1021/jm201504s

Schiefer, I. T.; Abdul-Hay, S.; Wang, H.; Vanni, M.; Qin, Z.; Thatcher, G. R. J. Inhibition of Amyloidogenesis by Nonsteroidal Anti-inflammatory Drugs and Their Hybrid Nitrates. Journal of Medicinal Chemistry, 2011, 54, 2293-2306. 10.1021/jm101450p.

Abdul-Hay, S.; Schiefer, I. T.; Chandrasena, R. E. P.; Li, M.; Abdelhamid, R.; Wang, Y.-T.; Tavassoli, E.; Michalsen, B.; Asghodom, R. T.; Luo, J.; Thatcher, G. R. J. NO-SSRIs: Nitric Oxide Chimera Drugs Incorporating a Selective Serotonin Reuptake Inhibitor. ACS Medicinal Chemistry Letters, 2011, 2, 656-661. 10.1021/ml2000033

Abdelhamid, R.; Luo, J.; VandeVrede, L.; Kundu, I.; Michalsen, B.; Litosh, V. A.; Schiefer, I. T.; Gherezghiher, T.; Yao, P.; Qin, Z.; Thatcher, G. R. J. Benzothiophene Selective Estrogen Receptor Modulators Provide Neuroprotection by a Novel GPR30-Dependent Mechanism. ACS Chemical Neuroscience, 2011, 2, 256-268. 10.1021/cn100106a

Anand, S.; Schiefer, I. T.; Thatcher, G.R. J. Nitric Oxide Donor and Mimetic Molecules in Cancer Chemotherapy and Chemoprevention. Forum on Immunological Diseases and Therapies, 2010, 1, 251-279. 10.1615/ForumImmunDisTher.v1.i4.20

Sinha, V.; Wijewickrama, G. T.; Chandrasena, R. E. P.; Xu, H.; Edirisinghe, P. D.; Schiefer, I. T.; Thatcher, G. R. J. Proteomic and Mass Spectroscopic Quantitation of Protein S-Nitrosation Differentiates NO-Donors. ACS Chemical Biology, 2010, 5, 667-680. 10.1021/cb100054m

Filed (in prosecution) and Issued Patents 

Reactive oxygen species-​sensitive nitric oxide synthase inhibitors for the treatment of ischemic stroke. Nash, K. M.; Schiefer, I.; Shah, Z.; (2019), US20190144377.

Furoxans as therapies for neurodegenerative disorders. Schiefer, I.; Shah, Z.; (2018), WO2018093762A1.

Novel cysteine protease inhibitors and uses. Arancio, Ottavio; Fa, Mauro; Schiefer, Isaac T.; Thatcher, Gregory; (2013), WO2013US24364 20130201. 

Last Updated: 8/6/20