The Department of Chemistry

Faculty

David G. Hangauer

David HangauerAssociate Professor
Office: 515 Natural Sciences Complex
Phone: (716) 645-4183
Fax: (716) 645-6963
E-mail: hangauer@buffalo.edu
Information on the Hangauer Research Group

 

 

Education:

  • Ph.D., University at Buffalo, 1980 (Organic Chemistry)

Awards and Honors:

  • “Outstanding Inventor Award”, May 20, 2002 from the Research Foundation of the State of New York for “outstanding inventions from superior research at the State University of New York”.
  • STOR 2004 “Entrepreneur” award for starting Kinex Pharmaceuticals LLC.
  • STOR 2004 “Entrepreneur” award for starting Molecular Target Laboratories LLC.
  • STOR 2004 “Visionary Innovator” award bestowed on May 26, 2005 for inventing technology licensed to Kinex Pharmaceuticals LLC.
  • “Licensed Innovation Award”, Nov. 3, 2005 from the Research Foundation of the State of New York for innovations that led to licensing agreements between the Research Foundation and companies.
  • James H. Crowdle Award Medal, Feb. 2006.  Award to an alumnus of the Canisius College Chemistry and Biochemistry Department that has made exceptional contributions to the field of chemistry and/or biochemistry.
  • 2005 Visionary Innovator Award, June 2006, from the University at Buffalo in recognition of licensing my invention "Protection Against Noise Or Cancer Drug-Induced Hearing Loss Using Inhibitors of pp60-c-src Protein Tyrosine Kinase" to Kinex Pharmaceuticals, LLC.
  • 2005 University at Buffalo Center for Advanced Biomedical and Bioengineering Technology Award, June 2006, in recognition of my collaboration with Kinex Pharmaceuticals, LLC on the research project "Development of a Src Inhibitor for the Treatment of Cancer".
  • Niagara Frontier Intellectual Property Law Association and the Technical Societies Council of the Niagara Frontier Health Sciences 2006 Inventor of the Year for U.S. patent 7,070,936 entitled "Method for Designing Protein Kinase Inhibitors".  Award announced on April 18, 2007.
  • Business First’s Health Care 50 Award published in Business First’s April 2007 issue honoring extraordinary professionals involved in the medical field.
  • Chair's Fellow for the 2007 Medicinal Chemistry Gordon Research Conference, Aug. 2007, Colby-Sayer College, New London, New Hampshire.
  • “Best Poster From An Academic Laboratory” 2007 Medicinal Chemistry Gordon Research Conference.
  • Niagara Frontier Intellectual Property Law Association and the Technical Societies Council of the Niagara Frontier Health Sciences 2007 Inventor of the Year for U.S. patent 7,300,931 entitled "Compositions for treating cell proliferation disorders".  This is the composition of matter and use patent for Kinex’s oncology drug KX2-391 currently in clinical trials.  Award announced on May 8, 2008.
  • Niagara Frontier Intellectual Property Law Association and the Technical Societies Council of the Niagara Frontier 2007 Inventor of the Year across all categories (i.e. Independent Inventors, Life Sciences & Physical Sciences) for U.S. patent 7,300,931 entitled "Compositions for treating cell proliferation disorders".  This is the composition of matter and use patent for Kinex’s oncology drug KX2-391 currently in clinical trials.  Award announced on May 8, 2008.
  • 66 Patents

Specializations:

Design and synthesis of protein kinase inhibitors as anti-cancer drugs, new methods, strategies and applications in combinatorial chemistry, and basic research in ligand-protein binding energetics

Research Summary:

A broad-based protein kinase inhibitor discovery program is in progress that utilizes computer-aided-drug design and combinatorial synthetic chemistry technologies. These two technologies represent the most advanced "rational" and "empirical" approaches to drug discovery, respectively. Combining the two technologies provides a synergistic approach to drug discovery that is at the cutting edge of Medicinal Chemistry. Each of these technologies overcomes the main weakness of the other.

The human body contains around 2,000 different protein kinases. These enzymes catalyze the transfer of the terminal phosphate from ATP to their protein substrates by forming a phosphate linkage at tyrosine or serine residues. Protein kinases are intimately involved in cell signaling. They control events such as cell proliferation, cell movement and programmed cell death (apoptosis). Abnormally elevated activity of various protein kinases is involved in a number of diseases, including cancer. Consequently, inhibitors of these individual protein kinases have the potential to be useful drugs. Our lab is currently focused upon discovering inhibitors of the tyrosine kinase pp60c-src because this enzyme is linked to the survival of cancer cells but is not necessary for the survival of normal cells. Inhibitors of pp60c-src offer four potential utilities for treating cancer. 1) Inhibition of uncontrolled cancer cell proliferation. 2) Inhibition of metastasis. 3) Inhibition of tumor angiogenesis. 4) Low toxicity.

We begin by designing prototype inhibitors of pp60c-src using molecular modeling and the crystal structures of various protein kinases. These initial inhibitors are then synthesized and tested for their biological activity. If the results are promising, a library of related inhibitors is designed, synthesized and tested. The synthesis of these libraries utilizes solid-supported combinatorial chemistry and an automated parallel reactor allowing 96 compounds to be simultaneously prepared.

Students and post-doctoral associates participate in the design, synthesis and interpretation of the biological activity of the compounds, thereby providing highly relevant training for a career in the pharmaceutical or biotechnology industry. Hands-on experience in combinatorial synthesis techniques is particularly sought after by employers in these industries. In addition, this training is received while working on a research project that has the potential to generate, in collaboration with industrial partners, drugs for serious diseases such as cancer. This project has a wide range of collaborators applying the latest molecular and cell biology technologies, including measuring gene expression profiles using DNA microarrays.

Other projects underway include the design and synthesis of novel scaffolds for the preparation of combinatorial libraries and basic research on the energetics of molecular recognition in biological assays.

Selected Recent Publications:

  1. R. Saperstein, P. P. Vicario, H. V. Strout, E. Brady, E. E. Slater, W. J. Greenlee, D. L. Ondeyka, A. A. Patchett, and D. G. Hangauer (1989). "Design of a Selective Insulin Receptor Tyrosine Kinase Inhibitor and Its Effect on Glucose Uptake and Metabolism in Intact Cells" Biochemistry, 28, 5694-5701.
  2. M. H. Kim, J. H. Lai & D. G. Hangauer (1994). "Tetrapeptide tyrosine kinase inhibitors: Enantioselective synthesis of p-hydroxymethyl-L-phenylalanine, incorporation into a tetrapeptide, and subsequent elaboration into p-(hydroxy-phosphonomethyl)-L-phenylalanine" Int. J. Peptide & Protein Res., 44, 457-465.
  3. Warren, S. D., Lee, B., Choi, S., Nair, S.A. & Hangauer, D. G. (1994). "Modified Assay Conditions and Results with Phosphorous Containing Peptide Inhibitors of Protein Kinase A (PKA)", FASEB Journal, 8, 1231.
  4. Shrikumar A. Nair, Bongyong Lee & David G. Hangauer (1995). "Synthesis of Orthogonally Protected L-Homocysteine and L-2-Amino-4-phosphonobutanoic Acid From L-Homoserine", Synthesis, 7, 810-814.
  5. Shrikumar A. Nair, Moon H. Kim, Zhou Songyang, Lewis C. Cantley & David G. Hangauer (1995). "Identification of an Efficient Pentapeptide Substrate for the Tyrosine Kinase pp60c-src", J. Med. Chem., 38, 4276-4283.
  6. Jack H. Lai, Ha Pham & David G. Hangauer (1996). "Synthesis of a Vicinal Tricarbonyl Amide Derivative of L-Phenylalanine", J. Org. Chem., 61, 1872-1874.
  7. Michael R. Pavia, Michael, P. Cohen, Garrett J. Dilley, Gloria R. Dubac, Tracy L. Durgin, Frank W.B Forman, Mark E. Hediger, Guy Milot, Timothy S. Powers, Irving Sucholeiki, Shulan Zhou & David G. Hangauer (1996). "The Design and Synthesis of Substituted Biphenyl Libraries", Bioorganic & Medicinal Chemistry, 4, 659-666.
  8. Jack H. Lai, Thomas H. Marsilje, Sun Choi, Shrikumar A. Nair & David G. Hangauer (1998). "The design, synthesis and activity of pentapeptide pp60c-src inhibitors containing L-phosphotyrosine mimics", J. Peptide Res., 51, 271-281.
  9. Gary K. Hsiao, David G. Hangauer (1998). "A Facile Synthesis of tert-Butyl 2-[(Benzyloxycarbonyl)amino]-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)propionate: An Orthogonally Protected Boronic Acid Analog of Aspartic Acid", Synthesis, July, 1043-1046.
  10. Thomas H. Marsilje, Karen L. Milkiewicz, and David G. Hangauer (2000). "The Design, Synthesis and Activity of Non-ATP Competitive Inhibitors of pp60c-src Tyrosine Kinase. Part 1: Hydroxynaphthalene Derivatives", Bioorg. Med. Chem. Lett., 10, 477-481.
  11. Karen L. Milkiewicz, Thomas H. Marsilje, Richard P. Woodworth Jr., Neil Bifulco Jr., Matthew J. Hangauer, and David G. Hangauer (2000). "The Design, Synthesis and Activity of Non-ATP Competitive Inhibitors of pp60c-src Tyrosine Kinase. Part 2: Hydroxyindole Derivatives", Bioorg. Med. Chem. Lett., 10, 483-486.

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The Department of Chemistry