Seth Rose

PSC -C241
PHYSICAL SCIENCE CENTER
TEMPE
Emeritus Professor
Faculty
Mailcode

Biography

 

Seth Rose's research is aimed at development of anticancer drugs designed to combat drug resistance by cancer cells. A principal mode of resistance is by cells pumping the drugs out by use of efflux pumps e.g., p-glycoprotein. Since most anticancer agents are inhibitors that bind reversibly to enzymes, the drugs are removed from the target enzyme and lose their effectiveness. To combat this, Rose's research group is designing enzyme inhibitors that covalently bind to key cellular targets in cancer cells, such as the proteins involved in cell division. Thus, interference with the target proteins will be irreversible even when excess (unbound) drug is removed from the cancer cell. Such cells will fail to move through cell division due to cell cycle arrest and subsequently undergo apoptosis, the process of self-disassembly of the cell. Currently, they are investigating agents targeting microtubules, as well as cyclin-dependent kinases and protein tyrosine phosphatase beta.

The chemical strategy that they are currently employing makes use of electrophilic functional groups that react with nucleophilic groups in proteins. For example, nucleophiles react by conjugate addition to an alpha, beta-unsaturated pi system (C=C-C=O) incorporated into their compounds. The other part of the compound is used to confer specificity to the biological binding site. Other compounds they are investigating contain an epoxide group, the three-membered ring electrophilic ether. These compounds effectively induce apoptosis in human cancer cells grown in culture. They employ molecular modeling to examine the structures of the synthetic compounds docked to the target biomolecules, with the intent of enhancing binding efficiency and selectivity, as well as optimization of covalent reactivity. The group synthesizes and studies the reactivity of the new compounds toward model electrophiles, and with the help of collaborators, evaluate compounds for efficiency of cancer cell growth inhibition in human cancer cells, including multidrug-resistant cell lines, as well as determine the stage of cell cycle arrest and the efficiency of induction of apoptosis. This work may lead to new agents that overcome development of drug resistance by cancer cells.

 

Education

Ph.D. University of California-San Diego 1974

Research Interests

Anticancer drug design: Seth Rose's research is aimed at development of anticancer drugs designed to combat drug resistance by cancer cells. A principal mode of resistance is by cells pumping the drugs out by use of efflux pumps e.g., p-glycoprotein. Since most anticancer agents are inhibitors that bind reversibly to enzymes, the drugs are removed from the target enzyme and lose their effectiveness. To combat this, Rose's research group is designing enzyme inhibitors that covalently bind to key cellular targets in cancer cells, such as the proteins involved in cell division. Thus, interference with the target proteins will be irreversible even when excess (unbound) drug is removed from the cancer cell. Such cells will fail to move through cell division due to cell cycle arrest and subsequently undergo apoptosis, the process of self-disassembly of the cell. Currently, they are investigating agents targeting microtubules, as well as cyclin-dependent kinases and protein tyrosine phosphatase beta.

The chemical strategy that they are currently employing makes use of electrophilic functional groups that react with nucleophilic groups in proteins. For example, nucleophiles react by conjugate addition to an alpha, beta-unsaturated pi system (C=C-C=O) incorporated into their compounds. The other part of the compound is used to confer specificity to the biological binding site. Other compounds they are investigating contain an epoxide group, the three-membered ring electrophilic ether. These compounds effectively induce apoptosis in human cancer cells grown in culture. They employ molecular modeling to examine the structures of the synthetic compounds docked to the target biomolecules, with the intent of enhancing binding efficiency and selectivity, as well as optimization of covalent reactivity. The group synthesizes and studies the reactivity of the new compounds toward model electrophiles, and with the help of collaborators, evaluate compounds for efficiency of cancer cell growth inhibition in human cancer cells, including multidrug-resistant cell lines, as well as determine the stage of cell cycle arrest and the efficiency of induction of apoptosis. This work may lead to new agents that overcome development of drug resistance by cancer cells.

Publications

  • S. D. Rose and R. F. Hartman. Modified Chalcone Compounds as Antimitotic Agents. U.S. Patent Number 8,552,066 issued October 8, 2013. (Application Serial No. 12/777212) (2013).
  • S. D. Rose, S. R. Ottersberg, K. J. Okolotowicz, D. E. Robinson, R. Hartman, and S. Lefler. Anticancer Agents Based on Prevention of Protein Prenylation. Canadian Patent Number 2,353,867, issued October 8, 2013 (2013).
  • H. Han, Y. Zhao, T. Cuthbertson, R. F. Hartman, and S. D. Rose. Cell Cycle Arrest and Apoptosis Induction by an Anticancer Chalcone Epoxide. Archiv der Pharmazie – Chemistry in Life Science (2010).
  • T. L. Groy, C. J. Fadgen, and S. D. Rose. Methyl (Z)-2-chloro-3-(2-methoxycarbonylphenyl)prop-2-enoate. Acta Crystallographica (2010).
  • S. D. Rose, S. R. Lefler, S. R. Ottersberg, A. Y. Kim, K. J. Okolotowicz, and R. F. Hartman. Anticancer Agents Based on Regulation of Protein Prenylation. U.S. Patent Application Serial No. 12/204585 (2009).
  • S.D. Rose. Sulfonium-salt Suicide Inhibition (SSSi) of Cancer Cell Division. Arizona Biomedical Research Commission Annual Report (2009).
  • Robinson, C., Hartman, R. F. and Rose, S. D. Emollient, Humectant, and Fluorescent a,ß-Unsaturated Thiol Esters for Long-Acting Skin Applications. Bioorganic Chemistry (2008).
  • Rose, S. D., Okolotowicz, K. J., Hartman, R. F., Houtchens, J. Conjugated Nitro Alkene Anticancer Agents Based on Isoprenoid Metabolism. U.S. Patent No. 7,312,191 (2007).
  • Rose, Seth. Eluding Drug Resistance in Cancer Chemotherapy. (2007).
  • Rose, Seth. Sulfonium-Salt Suicide Inhibition (SSSi) of Cancer Cell Division. (2007).
  • S. D. Rose and R. F. Hartman. Modified Chalcone Compounds as Antimitotic Agents. U.S. Patent Application Ser. No. 11/744027 (2007).
  • R Hartman, Seth Rose. Kinetics and Mechanism of the Addition of Nucleophiles to a,ß-Unsaturated Thiol Esters. Journal of Organic Chemistry (2006).
  • T Cuthbertson, T Groy, Seth Rose. 1,3-Bis(3,4,5-trimethoxyphenyl)-2,3-epoxypropanone: An Anticancer Chalcone Epoxide. Acta Crystallographica Section E (2005).
  • A Kim, D Robinson, K Okolotowicz, R Hartman, S Lefler, S Ottersberg, W Lee, Seth Rose. Inactivation of Protein Farnesyltransferase by Active-Site-Targeted Dicarbonyl Compounds. Arch. Pharm. Pharm. Med. Chem (2001).
  • Rose, S. D., Okolotowicz, K. J., Hartman, R. F., Houtchens, J. Conjugated Nitro Alkene Anticancer Agents Based on Isoprenoid Metabolism. U.S. Patent Application 11/941,914 (0).
  • Rose, S. D., Okolotowicz, K. J., Hartman, R. F., Houtchens, J. Conjugated Nitro Alkene Anticancer Agents Based on Isoprenoid Metabolism. U.S. Patent Application 12/777212 (0).
  • Rose, S. D., Okolotowicz, K. J., Hartman, R. F., Houtchens, J. Conjugated Nitro Alkene Anticancer Agents Based on Isoprenoid Metabolism. U.S. Patent No. 7,977,315 (Issued July 12, 2011) (0).
  • S. D. Rose and R. F. Hartman. Chalcone Compounds as Antimitotic Agents. U.S. Patent No. 7,714,025 (Issued May 11, 2010) (0).
  • S. D. Rose, S. R. Lefler, S. R. Ottersberg, A. Y. Kim, K. J. Okolotowicz, and R. F. Hartman. Anticancer Agents Based on Regulation of Protein Prenylation. U.S. Patent No. 7,423,170 (0).
  • S. D. Rose, S. R. Lefler, S. R. Ottersberg, A. Y. Kim, K. J. Okolotowicz, and R. F. Hartman. Anticancer Agents Based on Regulation of Protein Prenylation. U.S. Patent No. 7,943,665 (Issued May 17, 2011) (0).
  • S. D. Rose, S. R. Lefler, S. R. Ottersberg, A. Y. Kim, K. J. Okolotowicz, and R. F. Hartman. Anticancer Agents Based on Regulation of Protein Prenylation. U.S. Patent Application Serial No. 12/204585 (0).
  • S. D. Rose, S. R. Ottersberg, K. J. Okolotowicz, D. E. Robinson, R. Hartman, and S. Lefler. Anticancer Agents Based on Prevention of Protein Prenylation. U.S. Patent No. 7,344,851 (0).

Research Activity

Courses

Spring 2014
Course NumberCourse Title
CHM 434Advanced Organic Chemistry II
CHM 532Advanced Organic Chem II
Fall 2013
Course NumberCourse Title
CHM 231Elementary Organic Chemistry

Presentations

  • Rosemarie F. Hartman and Seth D. Rose. Toward Cancer Detection by Chemically Induced Dynamic Nuclear Polarization-MRI. Frontiers in Molecular Imaging, Univ. of Texas Southwestern Medical Center, Dallas TX (May 2013).
  • S. D. Rose, R. F. Hartman, H. Han, and Y. Zhao. Overcoming Drug Resistance in Cancer Cells. NW Regional Mtg/Rocky Mtn Regional Mtg Amer. Chem. Soc., Park City UT (Jun 2008).
  • Hartman, R, Zhao, Y, Han, H, Rose, Seth. Growth Inhibition of Pancreatic Cancer Cells in Vitro by a Chalcone Derivative. 6th Biannual AZ Biosciences Leadership Symposium, "Building Collaborations" (Jun 2006).
  • Rose, Seth. Research Proposal for Development and Testing of Skin-Binding Cosmetic Actives. Prospective commercial partner at Arizona Technologies Enterprises (AzTE) (Apr 2005).
  • Houtchens, J, Cuthbertson, T, Hartman, R, Pedretti, A, Lowe, M, Okolotowicz, K, Rose, Seth. Anticancer Drug Development Based on Interference with Protein Farnesylation. Arizona Cancer Research Symposium (Nov 2004).
  • Rose, Seth, Hartman, Rosemarie. Methodology for Covalent Immobilization of Cosmetic Actives on Skin. AzTE-sponsored meeting with local dermatology specialty-products company (Nov 2004).
  • Rose, Seth, Hartman, Rosemarie. Methodology for Covalent Immobilization of Cosmetic Actives on Skin. AzTE-sponsored meeting with major personal-care-products company (Oct 2004).
  • Hartman, R, Robinson, C, Rose, Seth. Methodology for the Covalent Immobilization of Sunscreens on Skin. European Society for Photobiology Conference on Photoprotection (May 2001).
  • Rose, Seth. Novel Inhibitors of Mitosis. World's Best Technologies Showcase