Brian Blagg Research

Education and Training

  • B.A. 1994 Chemistry and Environmental Studies, Sonoma State University
  • Ph.D. 1999 Organic Chemistry, University of Utah (C. Dale Poulter)
  • 1999-2002 NIH Postdoctoral Fellow, The Scripps Research Institute (Dale L. Boger)

Positions

  • 2014-Present Lester and Betty Mitscher Professor
  • 2002-2007 Assistant Professor of Medicinal Chemistry
  • 2007-2010 Associate Professor of Medicinal Chemistry
  • 2010-Present Professor of Medicinal Chemistry
  • 2004-Present Full Member, Kansas Cancer Center
  • 2006-Present Faculty of 1000, Biology

Awards

  • 2013 The University of Kansas: Leading Light Award
  • 2012 "Kentucky Colonel” by the Commonwealth of Kentucky
  • 2011 The University of Kansas Scholarly Achievement Award
  • 2009 American Chemical Society David W. Robertson Award in Medicinal Chemistry
  • 2006 American Cancer Society Research Scholar
  • 2005 The University of Kansas Center for Teaching Excellence Award

Journal Activities

  • 2011 Senior Editor, The Journal of Medicinal Chemistry
  • 2009 Guest Editor, Journal of Medicinal Chemistry, Centennial Issue
  • 2009 Guest Editor, Current Topics in Medicinal Chemistry, Chaperone Function & Inhibition
  • 2010 Guest Editor, Bioorganic and Medicinal Chemistry Letters, 20th Anniversary Issue
  • 2007-Present Editorial Board, Perspectives in Medicinal Chemistry
  • 2008-Present Editorial Board, Future Medicinal Chemistry
  • 2009-Present Editorial Advisory Board, ACS Medicinal Chemistry Letters

The 90 kDa heat shock proteins (Hsp90) are molecular chaperones that are required for the refolding of denatured proteins and the maturation of nascent polypeptides into their biologically active, three-dimensional structures. In fact, numerous proteins represented in all six hallmarks of cancer are dependent upon Hsp90 for conformational maturation. Hsp90 inhibition provides a combinatorial attack on multiple pathways responsible for malignant cell growth and proliferation. Consequently, Hsp90 has emerged as a promising target for the development of cancer chemotherapeutics.

Hsp90 contains two ATP binding sites, and in order to fold nascent polypeptides into biologically active proteins, Hsp90 catalyzes the hydrolysis of ATP. ATP hydrolysis provides the Hsp90 protein folding machinery the requisite energy for folding "client" proteins into their correct three-dimensional conformation. Disruption of this folding process results in the destabilization of Hsp90 "client" protein complexes, which leads to ubiquitination and proteasome-mediated degradation of the protein substrate.

The N-terminal ATP binding site is inhibited by the natural products, geldanamycin (GDA) and radicicol (RDC). Three derivatives of GDA are currently in clinical trials for the treatment of several cancers, whereas, RDC has proven to be inactive in vivo. Unfortunately, GDA exhibits poor solubility and the presence of the quinone moiety leads to cytotoxicity unrelated to Hsp90 inhibition. Therefore, there is tremendous need for the development of new, soluble, and selective inhibitors of the Hsp90 protein folding process. One molecule that we have designed is radamide. Radamide is a chimeric molecule composed of the quinone moiety of GDA and the resorcinol ring of RDC. In vitro, this molecule has proven to be a good inhibitor of Hsp90 and provides a rational starting point for the development of more potent compounds. In addition, we have developed radester and the macrocyclic variant, radanamycin. We are working towards the first isoform selective Hsp90 inhibitors using the recent solution of our co-crystal structures.

The C-terminal ATP binding site was only recently elucidated by one our collaborators, Len Neckers (National Cancer Institute), who demonstrated that the coumarin antibiotics, including novobiocin, inhibit the C-terminal ATP binding site and leads to the degradation of Hsp90 client proteins similar to that of N-terminal inhibitors. Unfortunately, novobiocin’s activity is not sufficient for further clinical evaluation and thus provides an opportunity for the development of more effective Hsp90 inhibitors. We have developed the most potent C-terminal inhibitors of Hsp90 yet discovered (A4 and DHN2) and have been able to demonstrate that Hsp90 inhibitors possess potent neuroprotective properties for potential use against Alzheimer’s, Parkinson’s, and Multiple Sclerosis. We have been able to separate neuroprotective activity from anti-cancer activity and are working vigilantly towards developing compounds suitable for clinical trials.

The major goals for members of the Blagg Research Team are to design, synthesize, and evaluate novel inhibitors of the Hsp90 protein folding process. To achieve these goals, we use computer modeling to design new molecules to bind to these ATP binding sites, we develop new organic reactions that allow access the desired compounds in a highly efficient manner, and finally we develop assays that are suitable for determining the biological effects of our rationally designed Hsp90 inhibitors. In addition, we are currently engaged in more than 30 collaborative studies with researchers throughout the world!

Front row (L to R): Dr. Qian Zhang, Rachel Davis, Leah Forsberg, Katherine Byrd
Back Row: (L to R): Antwan Girgis, Anuj Khandelwal, Eric Lightfoot, Vince Crowley, Sanket Mishra, Suman Gosh, Gaurav Garg, Zheng Zhang, Dr. Brian Blagg


Katherine Byrd earned a Ph.D. from the University of Notre Dame in May, 2015.  Under the supervision of Professor Paul Helquist, she worked on the design, synthesis and application of cholesterol-based molecular probes as biochemical tools for the study of cholesterol trafficking.  In August 2015, Katherine joined Dr. Blagg’s laboratory as a postdoctoral researcher.  She is working on the design and synthesis of novel C-terminal Hsp90 inhibitors.

Vince is a graduate student in the medicinal chemistry program.  He graduated with a bachelor’s degree in Chemistry from Creighton University in Omaha, Nebraska in 2012.  After joining the Blagg lab in January 2013, he has been working on the development of isoform selective N-terminal Hsp90 inhibitors.

Rachel Davis

Rachel Davis earned B.S. degrees in chemistry and biochemistry from Virginia Tech in Blacksburg, Virginia in May 2013. She joined Blagg lab as a graduate student in January 2014 and is working on the synthesis and evaluation of C-terminal Hsp90 inhibitors.

Leah Forsberg graduated with a bachelor's degree in chemistry from Luther College in Decorah, Iowa in 2011. She joined the Blagg lab in January 2012 and is working on the synthesis of novel C-terminal Hsp90 inhibitors.

Gaurav Garg graduated with a master’s degree in pharmaceutical chemistry form Uttar Pradesh Technical University, Lucknow, India in 2007. He joined Jubilant Chemysys, a pharmaceutical company as a research chemist on the design and synthesis of diversity-oriented molecules targeting GPCRs. In August 2011, he joined the Blagg laboratory as a graduate student and is working on the synthesis and evaluation of ring constrained C-terminal Hsp90 inhibitors.

Suman Ghosh

Suman Ghosh is researching cell polarity events in eukaryotic cells. He earned a Ph.D. in biological sciences from the University of Nebraska Lincoln (UNL) in 2009. During his PhD in the Nickerson Lab, he worked on morphogenesis of an opportunistic fungal pathogen Candida albicans and host-fungal interaction. He then worked as a postdoctoral research associate at Stowers Institute focusing on the functions of inner nuclear membrane SUN protein in chromosome segregation, nuclear organization important in premature aging, muscular dystrophy, and cancer. He joined Dr. Blagg’s laboratory as a post-doctoral researcher and  is working on the role of different isoforms of Hsp90 in cellular events relevant for cancer and diabetic neuropathy.

Antwan Girgis earned a B.S. in chemistry from Tanta University in Egypt in 2006. He joined Dr. Blagg’s lab in 2011 and worked on the synthesis of Novious Sugar and the synthesis and evaluation of Novologues as C-Terminal Hsp90 inhibitors.  He will graduate with a Pharm.D. degree from the University of Kansas Pharmacy School in May 2016. He contributed to multiple publications through Prof. Blagg’s lab, including “Novologues containing a benzamide side chain manifest anti-proliferative activity against two breast cancer cell lines.

Jessica Hall graduated in May of 2009 from Shorter College in Rome, GA with a B.S. in Chemistry and Biology. She joined Dr. Blagg’s group as a graduate student in January of 2010. Her projects involve the biochemical evaluation of Hsp90 inhibitors on the Hsp90 complex and potential small molecule modulators of SUMOylation.

Anuj Khandelwal

Anuj is a third year graduate student who earned his bachelor’s degree in chemistry in 2006 and master’s degree in organic chemistry in 2008 from the University of Delhi. He joined Dr. Blagg’s group in January of 2011. He is working on the development of EGCG analogues to inhibit Hsp90 and the development of isoform selective N-terminal Hsp90 inhibitors.

Eric Lightfoot

Eric Lightfoot double majored in biochemistry/biology at Southwestern College before transferring to KU. He was admitted into the University of Kansas School of Pharmacy in 2014. He is a first-year pharmacy student with interests in researching HSP90 protein inhibitors for the treatment of cancer, which was inspired by his mother's battle with cancer.

Sanket is a third-year graduate student in Dr. Blagg’s lab. He received his B.Pharm (2007) from the University of Mumbai, India and M.Pharm (2009) from Institute of Chemical Technology (formerly UDCT) Mumbai. Sanket also worked at Piramal Life Sciences Ltd Before joining Blagg’s group. His current project involves design, synthesis and biological evaluation of isoform selective inhibitors targeting the N-termius of Grp94.

Qian Zhang earned her Ph. D in January of 2004 from Fudan University of China in Medicinal Chemistry. She joined Dr. Blagg’s group as a visiting scholar in March of 2015 and currently she is working on the synthesis of C-terminal inhibitors of HSP90.

Zheng Zhang

Zheng Zhang graduated with a Ph.D. in chemistry from Northern Illinois University in DeKalb, Illinois in December 2014, where he worked on the development, synthesis and evaluation of novel IspF inhibitors as potential antibacterial and antimalarial agents, under the supervision of Dr. Timothy Hagen. He joined Dr. Brian Blagg’s research group as a post-doctoral researcher in February, 2015. He is working on the synthesis of novel C-terminal Hsp90 inhibitors.

Publications from the University of Kansas

  1. Zhao, H.; Kusuma, B.; Blagg, B. Probing the sugar binding pocket of Hsp90 C-terminus by second generation amine replacement of noviose on novobiocin scaffold. Manuscript in Preparation.
  2. Ma, J.; Farmer, K.; Pan, P.; Urban, M.; Zhao, H.; Blagg, B.; Dobrowsky, R. Heat Shock Protein 70 is Necessary to Improve Mitochondrial Bioenergetics and Reverse Diabetic Sensory Neuropathy Following KU-32 Therapy. Diabetes. Submitted.
  3. Hendricks, A.; Hanson, R.; Amolins, M.; Blagg, B. Synthesis and Preliminary Evaluation Steroidal Antiestrogen-Geldanamycin Conjugates. Bioorg. Med. Chem. Lett. 2013, 23, 3635-9.
  4. Khandelwal, A.; Hall, J.; Blagg, B. Synthesis and structure-activity relationships of EGCG analogues, a recently identified Hsp90 inhibitor. J Org Chem. 2013, 78, 7859-84.
  5. Eskew, J.; Sadikot,T.; Brown, D.; Rajewski, R.; Blagg, B.; Matts, R.; Holzbeierlein, J.;Vielhauer, G. Development of a high-throughput screening cancer cell based luciferase refolding assay for identifying Hsp90 inhibitors. Assay Drug Dev. Technol. 2013, 23, 3635-9
  6. Pathwardhan, C.; Fauq, A.; Peterson, L.; Miller, C.; Blagg, B.; Chadli, A. Gedunin Inactivates the Co-Chaperone p23 Causing Breast Cancer Cell Death by Apoptosis. J. Biol. Chem. 2013, 288, 7313-25.
  7. Zhao, H.; Moroni, E.; Yan, B.; Colombo, G.; Blagg, B. 3D-QSAR Assisted Design, Synthesis and Evaluation of Novobiocin Analogues. ACS Med Chem Lett. 2013, 4, 57–62.
  8. Zhao, H.; Blagg, B. Novobiocin analogues with second-generation noviose surrogates. Bioorg. Med. Chem.Lett. 2013, 23, 552-7.
  9. Diaz, F.; McDonald, P.; Roy, A.; Taylor, B.; Price, A.; Hall, J.; Blagg, B.; Chaguturu, R. Compound ranking based on a new mathematical measure of effectiveness using time course data from cell-based assays. Comb. Chem. High Throughput Screening. 2013, 16, 168-79.
  10. Iwai, A.; Bourboulia, D.; Mollapour, M.; Jensen-Taubman, S.; Lee, S.; Donnelly, A.; Yoshida, S.; Miyajima, N.; Tsutsumi, S.; Smith, A.; Sun, D.; Wu, X.; Blagg, B.; Trepel, J.; Stetler-Stevenson, W.; Neckers, L. Combined inhibition of Wee1 and Hsp90 activates intrinsic apoptosis in cancer cells. Cell Cycle. 2012, 11, 3649-55.
  11. Kusuma, B.; Brandt, G.; Blagg, B. Synthesis of Cruentaren A. Organic Letters. 2012, 14, 6242-5.
  12. Farmer, K.; Williams, J.; Novikova, L.; Ramachandran, K.; Rawal, S.; Dobrowsky, R.; Blagg, B.; Stehno-Bittel, L. Ku-32, a Novel Drug for Diabestic Neuropathy, is Safe for Human Islets and Improves in Vitro Insulin Secretion and Viability. Exp. Clin. Endocrinol. Diabetes. 2012,1, 1-11.
  13. Li, C.; Ma, J.; Zhao, H.; Blagg, B.; Dobrowsky, R. Induction of Heat Shock Protein 70 (Hsp90) Prevents Neuregulin-Induced Demyelination by Enhancing the Proteasomal Clearance of c-Jun. ASN Neuro. 2012, 4, 425-37.
  14. Suntharalingam, A.; O’Leary, J.; Koren, J.; Blair, L.; Hill, S.; Abisambra, J.; Jinwal, U.; Cockman, M.; Duerfeld, A.; Tomarev, S.; Blagg, B.; Lieberman, R.; Dickey, C. Grp94 triage of mutant myocilin through ERAD subverts a more efficient autophagic clearance mechanism. J Biol Chem. 2012, 287, 40661-9.
  15. Duerfeldt, A.; Peterson, L.; Maynard, J.; Shinogle, H.; Moore, D.; Gewirth, D.; Argon, Y.; Nicchitta, C.; Blagg, B. Development of a Grp94 Inhibitor. J. Am. Chem. Soc. 2012, 134, 9796–804.
  16. Urban, M.; Pan, P.; Farmer, K.; Zhao, H.; Blagg, B.; Dobrowsky, R. Modulating molecular chaperones improves sensory fiber recovery and mitochondrial function in diabetic peripheral neuropathy. Exp Neurol. 2012, 235, 388-96.
  17. Peterson, L.; Eskew, J.; Vielhauer, G.; Blagg, B. The hERG channel is dependent upon the Hsp90α isoform for maturation and trafficking. Mol. Pharm. 2012, 9, 1841-6.
  18. Kusuma, B.; Zhang, L.;Sundstrom, T.; Peterson, L.; Dobrowsky, R.; Blagg, B. Synthesis and Evaluation of Novologues as C-Terminal Hsp90 Inhibitors with Cytoprotective Activity against Sensory Neuron Glucotoxicity. J. Med. Chem. 2012, 55, 5795-812.
  19. Mark. C.; Mukerji, R.; Samadi, A.; Zhao, H.; Blagg, B.; Cohen, M. Novel C-Terminal Hsp90 Inhibitor for Head and Neck Squamous Cell Cancer (HNSCC) with in vivo Efficacy and Improved Toxicity Profiles Compared with Standard Agents. Ann. Surg. Oncol. 2012, 19, 483-90.
  20. Zhang, L.; Blagg, B.; Dobrowsky, R. A C-Terminal Heat Shock Inhibitor Decreases Hyperglycemia-induced Stress and Improves Mitochondrial Bioenergetics in Sensory Neurons. J. Proteome Res. 2012, 11, 2581–93.
  21. Zhao, H.; Yan, B.; Peterson, L.; Blagg, B. 3-Arylcoumarin derivatives manifest anti-proliferative activity through Hsp90 inhibition. ACS Med. Chem. Lett. 2012, 3, 327–31.
  22. Li, K.; Frankowski, K.; Belon, C.; Neuenswander, B.; Ndjomou, J.; Hanson, A.; Shanahan, M.; Schoenen, F.; Blagg, B.; Aube, J.; Frick, D.; Optimization of Potent Hepatitis C Virus NS3 Helicase Inhibitors Isolated from the Yellow Dyes Thioflavine S and Primuline. J. Med. Chem. 2012, 55, 3319–30.
  23. Urban, M.; Dobrowsky, R.; Blagg, B. Heat shock response and insulin-associated neurodegeneration. Trends Pharmacol Sci. 2012, 3, 129–37.
  24. Samadi, A.; Zhang, X.; Mukerji, R.; Donnelly, A.; Blagg, B.; Cohe, M. A novel C-terminal HSP90 inhibitor KU135 induces apoptosis and cell cycle arrest in melanoma cells. Cancer Lett. 2011, 312, 158-67.
  25. Kusuma, B.; Duerfeldt, A.; Blagg, B. Synthesis and biological evaluation of non-hydolysable novobiocin analogues as C-terminal Hsp90 inhibitors. Bioorg. Med. Chem. Lett. 2011, 21, 7170-4.
  26. Eskew, J.; Sadikot, T.; Morales, P.; Duren, A.; Dunwiddie, I.; Swink, M.; Zhang, X.; Hembruff, S.; Donnelly, A.; Rajewski, R. BMC Cancer. 2011, 11, 468.
  27. Brandt, G. and Blagg, B. Monoenomycin: A simplified trienomycin A analogue that manifests anticancer activity. ACS Med. Chem. Lett. 2011, 2, 735-40.
  28. Kusuma, B.; Peterson, L.; Zhao, H.; Veilhauer, G.; Holzbeierlein, J.; Blagg, B.; Targeting the Heat Shock Protein 90 Dimer with Dimeric Inhibitors. J. Med. Chem. 2011, 18, 6234-6253.
  29. Matts, R.; Dixit, A.; Peterson, L.; Sun, L.; Voruganti, S.; Kalyanaraman, P.; Hartson, S.; Blagg, B. Elucidation of the Hsp90 C-terminal inhibitor binding site. ACS Chem. Biol. 2011, 6, 800–7.
  30. Zhao, H; Donnelly, A.; Kusuma, B.; Brandt, G.; Brown, D.; Rajewski, R.; Vielhauer, G.; Holzbeierlein, J.; Blagg, B. Engineering an antibiotic to fight cancer: Optimization of the
    novobiocin scaffold to produce anti-proliferative agents. J. Med. Chem. 2011, 54, 3839–53.
  31. Blagg, B.; Johnson, D.; Garbaccio, R. Recent advances in Medicinal Chemistry. Bioorg. Med. Chem. Lett. 2011, 21, 2585-6.
  32. Davenport, J.; Manjarrez, J.; Peterson, L.; Blagg, B.; Matts, R. Gambogic acid, a natural product inhibitor of Hsp90. J. Nat. Prod. 2011, 74, 1085–92.
  33. Zhao, H.; Brandt, G.; Lakshmi, G.; Matts, R.; Blagg, B. Identification and initial SAR of silybin: An Hsp90 inhibitor. Bioorg. Med. Chem. Lett. 2011, 21, 2659–64.
  34. Guarnieri M.; Blagg B.; Zhao R.; A High-Throughput TNP-ATP Displacement Assay for Screening Inhibitors of ATP-Binding in Bacterial Histidine Kinases. Assay Drug Dev Techn. 2011, 9, 174-8.
  35. Matts, R.; Brandt, G.; Lu, Y.; Dixit, A.; Mollapour, M.; Wang, S.; Donnelly, A.; Neckers, L.; Verkhivker, G.; Blagg, B. A systematic protocol for the characterization of Hsp90 modulators. Bioorg. Med. Chem. Lett. 2011, 19, 684-92.
  36. Urban, M.; Chengyuan, L.; Yu, C.; Pan, P.; Lu, Y.; Krise, J.; McIntosh, M.; Rajewski, R.; Blagg, B.; Dobrowsky, R. Inhibiting heat-shock protein 90 reverses sensory hypoalgesia in diabetic mice. ASN Neuro. 2010, 2, 189-99.
  37. Peterson, L. and Blagg, B. Click chemistry to probe Hsp90: Synthesis and evaluation of a series of triazole-containing novobiocin analogs. Bioorg. Med. Chem. Lett. 2010, 20, 3957-60.
  38. Duerfeldt, A. and Blagg, B. Hsp90 Inhibition: Elimination of shock and stress. Bioorg. Med Chem. Lett. 2010, 20, 4983-7.
  39. Guarnieri, M.; Blagg, B.; Zhao, R. High-Throughput TNP-ATP Displacement Assay for Screening Inhibitors of ATP-Binding in Bacterial Histidine Kinases. Assay Drug Dev Technol. 2010, 9, 174-83.
  40. Mollapour, M.; Tsutsumi, S.; Donnelly, A.; Beebe, K.; Tokita, M.; Lee, M.; Lee, S.; Morra, G.; Bourboulia, D.; Scroggins, B.; Colombo, G.; Blagg, B.; Panaretou, B.; Stetler-Stevenson, W.; Trepel, J.; Piper, P.; Prodromou, C.; Pearl, L.; Neckers, L. Swe1/Wee1-dependent tyrosine phosphorylation of Hsp90 regulates distinct facets of chaperone function. Mol. Cell. 2010, 37, 333-43.
  41. Cunningham, C.; Mukhopadhyay, A.; Wiredu, B.; Blagg, B.; Prisinzano, T.; Krise, J. Distribution and Diffusivity of Reactive Flurophores in Cells: Implications toward Target Identification. Mol. Pharmaceutics. 2010, 7, 1301-10.
  42. Matthews, S.; Vielhauer, G.; Manthe, C.; Chaguturu, V.; Szabla, K.; Matts, R.; Donnelly, A.; Blagg, B.; Holzbeierlein, J. Characterization of a novel novobiocin analogue as a putative C-terminal inhibitor of heat shock protein 90 in prostate cancer cells. Prostate. 2010, 70, 27-36.
  43. Zhao, H.; Kusuma, B.; Blagg, B. Synthesis and Evaluation of Noviose Replacements on Novobiocin That Manifest Antiproliferative Activity. ACS Med. Chem. Lett. 2010, 1, 311-5.
  44. Donnelly, A.; Zhao, H.; Kusuma, B.; Blagg, B. Cytotoxic sugar analogues of an optimized novobiocin scaffold. MedChemComm. 2010, 1, 165-70.
  45. Jadhav, V.; Duerfeldt, A.; Blagg, B. Design, synthesis, and biological activity of bicyclic radester analogues as Hsp90 inhibitors. Bioorg. Med. Chem. Lett. 2009, 19, 6845-50.
  46. Brandt, G. and Blagg, B. Alternated Strategies of Hsp90 Modulation for the treatment of Cancer and other diseases. Curr. Med. Chem. 2009, 9, 1447-61.
  47. Blagg, B. Inhibition and function of heat shock proteins 70 and 90. Curr. Top. Med. Chem. 2009, 9, 1335-6.
  48. Duerfeldt, A. and Blagg, B. Hydrating for Resistance to Radicicol. ACS Chem. Biol. 2009, 4, 245-7.
  49. Immormino, R.; Metzger IV, L.; Reardon, P.; Dollins, E.; Blagg, B.; Gewirth, D. Poses for Ligand and Chaperone in Inhibitor-Bound Hsp90 and GRP94: Implications for Paralog-Specific Drug Design. J. Mol. Biol. 2009, 388, 1033-42.
  50. Mays, J.; Hill, S.; Moyers, J.; Blagg, B. The synthesis and evaluation of flavone and isoflavone chimeras of novobiocin and derrubone. Bioorg. Med. Chem. Lett.. 2010, 18, 249-66.
  51. Peterson, L. and Blagg, B. To fold or not to fold: Modulation and consequences of Hsp90 inhibition. Future Med. Chem. 2009, 1, 267-83.
  52. Hadden, K. and Blagg, B. Synthesis and evaluation of radamide analogues, a chimera of radicicol and geldanamycin. J. Org. Chem. 2009, 74, 4697-704.
  53. Amolins, M. and Blagg, B. Natural Product Inhibitors of Hsp90: Potential Leads for Drug Discovery. Mini-Reviews in Medicinal Chemistry. 2009, 9, 140-52.
  54. Duerfeldt, A.; Brandt, G.; Blagg, B. Design, Synthesis and Biological Evaluation of Conformationally Constrained cis-Amide Hsp90 Inhibitors. Org. Lett. 2009, 11, 2353-6.
  55. Lu, Y.; Ansar, S.; Michaelis, M.; Blagg, B. Neuroprotective Activity and Evaluation of Hsp90 Inhibitors in An Immortalized Neuronal Cell Line. Bioorg. Med. Chem. Lett. 2009, 17, 1709-15.
  56. Hadden, K.; Hill, S.; Davenport, J.; Matts, Robert L.; Blagg, B. Synthesis and evaluation of Hsp90 inhibitors that contain the 1,4-naphthoquinone scaffold. Bioorg. Med. Chem. Lett. 2009, 17, 634-40.
  57. Shelton, S.; Shawgo, M.; Matthews, S.; Lu, Y.; Donnelly, A.; Szabla, K.; Tanol, M.; Vielhauer, G.; Rajewski, R.; Matts, R.; Blagg, B.; Robertson, J. KU135, a novel novobiocin-derived C-terminal inhibitor of the 90-kDa heat shock protein, exerts potent antiproliferative effects in human leukemic cells. Mol. Pharm. 2009, 76, 1314-22.
  58. Amolins, M.; Peterson, L.; Blagg, B. Synthesis and Evaluation of Electron Rich Curcumin Analogues. Bioorg. Med. Chem. Lett. 2009, 17, 360-7.
  59. Hirsch, J.; Rohr, M.; Patton, B.; Herre, W.; Inciardi, A.; Blagg, B.; Cohen, M. A Novel Small Molecule HSP90 Inhibitor With Antiproliferative Effects in Differentiated and Anaplastic Thyroid Cancers. Journal of Surgical Research. 2008, 144, 198.
  60. Donnelly, A.; Mays, J.; Burlison, J.; Nelson, J.; Vielhauer, G.; Holzbeierlein, J.; Blagg, B. The Design, Synthesis and Evaluation of Coumarin Ring Derivatives of the Novobiocin Scaffold that Exhibit Anti-proliferative Actvity. J. Org. Chem. 2008, 73, 8901-20.
  61. Brandt, G.; Schmidt, M.; Prisinzano, T.; Blagg, B. Gedunin, a novel Hsp90 inhibitor: semisynthesis of derivatives and preliminary structure-activity relationships. J. Med. Chem. 2008, 51, 6495-502.
  62. Donnelly, A. and Blagg, B. Novobiocin and Additional Inhibitors of the Hsp90 C-terminal Nucleotide-binding Pocket. Curr. Med. Chem. 2008, 15, 2702-17.
  63. Wang, M. and Blagg, B. Synthesis of a versatile metacyclophane macrolactam. Tetrahedron Letters. 2008, 49, 141-4.
  64. Hadden, M. and Blagg, B. Dimeric Approaches to Anticancer Chemotherapeutics. Invited review for Anti-cancer Agents Med. Chem. 2008, 8, 807-16.
  65. Burlison, J.; Avila, C.; Vielhauer, G.; Lubbers, D.; Holzbeierlein, J.; Blagg, B. Development of Novobiocin Analogues That Manifest Anti-proliferative Activity against Several Cancer Cell Lines. J. Org. Chem. 2008, 73, 2130-7.
  66. Hastings, J.; Hadden, M.; Blagg, B. Synthesis and Evaluation of Derrubone and Select Analogues. J. Org. Chem. 2008, 73, 369-73.
  67. Tash, J.; Chakrasali, R.; Jakkaraj, S.; Hughes, J.; Smith, K.; Hornbaker, K.; Heckert, L.; Ozturk, S.; Hadden, K.; Kinzy, T.; Blagg, B.; Georg, G. Gamendazole, an Orally Active Indazole Carboxylic Acid Male Contraceptive Agent, Targets HSP90AB1 (HSP90BETA) and EEF1A1 (eEF1A), and Stimulates Il1a Transcription in Rat Sertoli Cells. Biol Reprod. 2008, 78, 1139-52.
  68. Hadden, M.; Galam, L.; Gestwicki, J.; Matts, R.; Blagg, B. Derrubone, an Inhibitor of the Hsp90 Protein Folding Machinery. J. Nat. Prod. 2007, 70, 2014-8.
  69. Hadden, M. and Blagg, B. Cytotoxic small molecule dimers and their inhibitory activity against human breast cancer cells. Bioorg. Med. Chem. Lett. 2007, 17, 5063-7.
  70. Bishop, S.; Burlison, J.; Blagg, B. Hsp90: A Novel Target for the Disruption of Multiple Signaling Cascades. Invited Review for Current Cancer Drug Targets. 2007, 7, 369-88.
  71. Huang, Y. and Blagg, B. A Library of Noviosylated Coumarin Analogues. J. Org. Chem. 2007, 72, 3609-13.
  72. Blagg, B.; Hong, K.; Galam, L.; Richter, M.; Matts, R. The Role of Curcumin: An Unfolding Story. Acs. Chem. Biol. 2007,
  73. Galam, L.; Hadden, M.; Ma, Z.; Ye, Q.; Yun, B.; Blagg, B.; Matts, R. High-throughput assay for the identification of Hsp90-inhibitors based on Hsp90-dependent refolding of firefly luciferase. Bioorg. Med. Chem. 2007, 15, 1939-46.
  74. Ansar, S.; Burlison, J.; Hadden, M.; Yu, X.; Desino, K.; Bean, J.; Neckers, L.; Audus, K.; Michaelis, M.; Blagg, B. A Non-toxic Hsp90 Inhibitor Protects Neurons from Ab-induced Toxicity. Bioorg. Med. Chem. Lett. 2007, 17, 1984-90.
  75. Burlison, J.; Neckers, L.; Smith, A.; Maxwell, A.; Blagg, B. Novobiocin: Redesigning DNA Gyrase Inhibitors for Selective Inhibition of Hsp90. J. Am. Chem. Soc. 2006, 128, 15529-36.
  76. Burlison, J. and Blagg, B. Coumermycin A1 Analogues that Inhibit the Hsp90 Protein Folding Machinery. Org. Lett. 2006, 8, 4855-8.
  77. Shen, G.; Wang, M.; Welch, T.; Blagg, B. Design, Synthesis and Structure - Activity Relationships for Chimeric Inhibitors of Hsp90. J. Org. Chem. 2006, 71, 7618-31.
  78. Hadden, M.; Lubbers, D.; Blagg, B. Geldanamycin, Radicicol, and Chimeric Inhibitors of the Hsp90 N-terminal ATP Binding Site. Curr. Topics Med. Chem. 2006, 6, 1173-82.
  79. Chaudhury, S.; Welch, T.; Blagg, B. Hsp90 as a Target for Drug Development. ChemMedChem. 2006, 1, 1331-40.
  80. Duvvuri, M.; Konkar, S.; Hong, K.; Blagg, B.; Krise, J. A New Approach for Enhancing Differential Selectivity of Drugs to Cancer Cells. ACS Chem. Biol. 2006, 1, 309-15.
  81. Avila, C.; Hadden, M.; Ma, Z.; Kornilayev, B.; Ye, Q.; Blagg, B. High-throughput Screening for Hsp90 ATPase Inhibitors. Bioorg. Med. Chem. Lett. 2006, 16, 3005-8.
  82. Wang, M.; Shen, G.; Blagg, B. Radanamycin, A Macrocyclic Chimera of Radicicol and Geldanamycin. Bioorg. Med. Chem. Lett. 2006, 16, 2459-62.
  83. Peng, W. and Blagg, B. A Versatile Approach Toward the Ansamycin Antibiotics. Org. Lett. 2006, 8, 975-8.
  84. Avila, C.; Kornilaev, B.; Blagg, B. Development and Optimization of a Useful Assay for Determining Hsp90’s Inherent ATPase Activity. Bioorg. Med. Chem. 2006, 14, 1134-42.
  85. Blagg, B. and Kerr, T. Hsp90 Inhibitors: Small Molecules that Transform the Hsp90 Protein Folding Machinery into a Catalyst for Protein Degradation. Med. Res. Rev. 2006, 26, 310-38.
  86. Yu, X.; Shen, G.; Neckers, L.; Blake, H.; Holzbeierlein, J.; Cronk, B.; Blagg, B. Hsp90 Inhibitors Identified from a Library of Novobiocin Analogues. J. Am. Chem. Soc. 2005, 127, 12778-9.
  87. Yu, X.; Han, H.; Blagg, B. Synthesis of Mono- and Dihydroxylated Furanoses, Pyranoses, and an Oxepanose for the Preparation of Natural Product Analogue Libraries. J. Org. Chem. 2005, 70, 5599-605.
  88. Shen, G. and Blagg, B. Radester, A Novel Inhibitor of the Hsp90 Protein Folding Machinery. Org. Lett. 2005, 7, 2157-60.
  89. Clevenger, R. and Blagg, B. Design, Synthesis, and Evaluation of a Radicicol and Geldanamycin Chimera, Radamide. Org. Lett. 2004, 6, 4459-62.
  90. Shen, G.; Yu, X.; Blagg, B. Syntheses of Photolabile Novobiocin Analogues. Bioorg. Med. Chem. Lett. 2004, 14, 5903-6.
  91. Yu, X.; Shen, G.; Blagg, B. Synthesis of (-)-Noviose from 2,3-O-Isopropylidene-D-erythronolactol. J. Org. Chem. 2004, 7375-8.
  92. Clevenger, R.; Raible, J.; Peck, A.; Blagg, B. Biotinylated Geldanamycin. J. Org. Chem. 2004, 69, 4375-80.

Patents and Patent applications

  1. Blagg, B. Novobiocin analogues. University of Kansas, 2012: US 8212011
  2. Blagg, B. and Duerfeldt, A. Grp94 Inhibitors. U.S. Provisional Patent, 2011: 14288.0011USP1
  3. Blagg, B. and Kusuma, B. Dynamic Inhibitors of Heat Shock Protein 90 (HSP90). U.S. Provisional patent Serial, 2011: 61/488,321
  4. Calvet, J., Blagg, B.; Sunder, S.; Magenheiemer, B. Prepration of novobiocin analogs and treatment of polycystic kidney disease. PCT Int. Appl., 2011: WO 2011041593 A1 20110407.
  5. Blagg, B.; Zhao, H.; Donnelly, A. Novobiocin analogues having modified sugar moieties. 2010: WO2010096650.
  6. Blagg, B. Preparation of novobiocin analogs useful for treatment and/or prevention of neurodegenerative disorders, autoimmune disorders, and as antitumor agents. U.S. Pat. Appl. Publ., 2009, Ser. No. 801,473. CODEN: USXXCO US 2009187014 A1 20090723 CAN 151:173770 AN 2009:889014 CAPLUS
  7. Blagg, Brian. Preparation of novobiocin analogs having modified glycoside moieties as antitumor agents. U.S. Pat. Appl. Publ. (2009), 126pp., Cont.-in-part of U.S. Ser. No. 2007-801,473. CODEN: USXXCO US 2009163709 A1 20090625 CAN 151:78385 AN 2009:768091 CAPLUS
  8. Blagg, Brian; Michaelis, Mary Lou; Mcintosh, Michelle. Preparation of novobiocin analogs as anticancer agents. U.S. Pat. Appl. Publ. (2007), 64pp., Cont.-in-part of U.S. Ser. No. 266,149. CODEN: USXXCO US 2007270452 A1 20071122 CAN 147:522511 AN 2007:1334170 CAPLUS
  9. Blagg, Brian S.; Neckers, Len; Yu, Xiao Ming. Preparation of novobiocin analogs as anticancer agents. PCT Int. Appl. (2006), 66 pp. CODEN: PIXXD2 WO 2006050501 A2 20060511 CAN 144:450869 AN 2006:438069 CAPLUS
  10. Blagg, Brian; Shen, Gang; Clevenger, Randell C. Preparation of compounds having a quinone-like moiety and a dihydroxyphenol-like moiety as inhibitors of heat shock protein 90. U.S. Pat. Appl. Publ. (2006), 41 pp. CODEN: USXXCO US 2006089495 A1 20060427 CAN 144:432560 AN 2006:388754 CAPLUS

Postdoctoral Studies

  1. Elliott, G. I.; Fuchs, J. R.; Blagg, B. S. J.; Ishikawa, H.; Tao, H.; Yuan, Z.-Q.; Boger, D. L. Intramolecular Diels-Alder/1,3-Dipolar Cycloaddition Cascade of 1,3,4-Oxadiazoles. J. Am. Chem. Soc. 2006, 128, 10589-95.
  2. Blagg, B. S. J.; Boger, D. L. Total Synthesis of (+)-Camptothecin. Tetrahedron 2002, 58, 6343-9.
  3. Wilkie, G. D.; Elliott, G. I.; Blagg, B. S. J.; Wolkenberg, S. E.; Soenen, D. R.; Miller, M. M.; Pollack, S.; Boger, D. L. Intramolecular Diels-Alder and Tandem Intramolecular Diels-Alder/1,3-Dipolar Cycloaddition Reactions of 1,3,4-Oxadiazoles. J. Am. Chem. Soc. 2002, 124, 11292-4.

Graduate Studies

  1. Blagg, B. S. J.; Jarstfer, M. B.; Rogers, D. H.; Poulter, C. D. Recombinant Squalene Synthase. A Mechanism for the Rearrangement of Presqualene Diphosphate to Squalene. J. Am. Chem. Soc. 2002, 124, 8846-53.
  2. Koppisch, Andrew T.; Fox, David T.; Blagg, Brian S. J.; Poulter, C. D. E. coli MEP Synthase: Steady-State Kinetic Analysis and Substrate Binding. Biochemistry 2002, 236-43.
  3. Hahn, F.M.; Eubanks, L.M.; Testa, C.A.; Blagg, B.S.J.; Baker, J.A.; Poulter, C.D. 1-Deoxy-D-xylulose 5-phosphate Synthase, the Gene Product of Open Reading Frame (ORF) 2816 and ORF 2895 in Rhodobacter Capsulatus. J. Bacteriol. 2001, 183, 1-11.
  4. Koppisch, A. T.; Blagg, B. S. J.; Poulter, C. D. Synthesis of 2-C-Methyl-D-erythritol-4-phosphate: The First Pathway-Specific Intermediate in the Methylerythritol Phosphate Route to Isoprenoids. Org. Lett. 2000, 2, 215-7.
  5. Blagg, B. S. J.; Poulter, C. D. Synthesis of 1-Deoxy-D-xylulose and 1-Deoxy-D-xylulose-5-phosphate. J. Org. Chem. 1999, 64, 1508-11.
  6. Jarstfer, M. B.; Blagg, B. S. J.; Rogers, D. H.; Poulter, C. D. Biosynthesis of Squalene. Evidence for a Tertiary Cyclopropylcarbinyl Cationic Intermediate in the Rearrangement of Presqualene Diphosphate to Squalene. J. Am. Chem. Soc. 1996, 118, 13089-90. (Chemical and Engineering News, January 6, 1997, News of the week: "Biosynthesis of Squalene.")

Doctoral Program Profiles

The University of Kansas is a major public research and teaching institution with a number of doctoral degree programs. Visit the profiles page which provides summary data for Lawrence-campus doctoral programs as one-page doctoral program profiles.

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