Specialized Chemistry Center

Program Summary

As described by the NIH, "The Molecular Libraries Program (MLP), a component of the NIH Common Fund, offers public sector biomedical researchers access to the large-scale screening capacity necessary to identify small molecules that can be optimized as chemical probes to study the functions of genes, cells, and biochemical pathways. The Molecular Libraries Probe Production Centers Network (MLPCN), as part of the MLP, is a nationwide consortium of small molecule centers that produces innovative chemical tools for use in biological research." In September 2008, the University of Kansas received a six-year, $20.2 million research award from the National Institutes of Health to establish a Specialized Chemistry Center (KU SCC). As part of the NIH MLPCN, the mission of the KU SCC was to develop probes based on hits uncovered in NIH screening efforts. This project ended in May 2015.

Program Information

Core A: Administration

Core A was responsible for the coordination of all scientific activities of the Specialized Chemistry Core, manage personnel and intellectual property matters, and administer its budget. 

Core B: Synthesis/Purification Core

Core B was responsible for planning and executing medicinal chemistry projects presented to the SCC by the MLPCN leadership with the aid of core C (which provided computational chemistry and cheminformatics support ),  by purifying compounds and providing essential analytical chemistry validation, and coordinating the submission of compounds to the compound repository.  

Core C: Cheminformatics Core

Core C applied a series of computational protocols to efficient delivery of chemical insight that guided targeted synthesis of hit analogs with elevated prospects for achieving probe status. 

Chemical Tools and Methods for Identification of Targets of Biologically Active Small Molecules

Aim 1: Develop methodology for visualizing and identifying intracellular targets using fluorescently labeled probes - Brian Blagg, Jeffrey Krise, and Thomas Prisinzano, Project Leaders

Aim 2: Development of yeast three-hybrid (Y3H) systems as tools for the identification of protein targets of small molecules – Blake Peterson, Project Leader.

Synthesis Formats

  • Solution-phase
  • Solution-phase using solid-phase reagents or scavengers
  • Solid-phase

Synthesis Capabilities

  • Serial
  • Parallel
  • Combinatorial
  • Microwave

Analysis, Purification and Compound Management Capabilities

  • High-throughput analytical-scale RP HPLC/photodiode array UV/HRMS
  • High-throughput mass-directed preparative-scale RP HPLC/dual-wavelength UV/LRMS/ELSD
  • Medium-throughput, automated, 5mm tube-based 1H and 13C NMR
  • Compound formatting available in a variety of formats (vials, plates) and solvents

Cheminformatics Capabilities

  • Virtual compound library enumeration and screening
  • In silico property calculation, including ADME, toxicology, and metabolic profiling
  • Pharmacophore perception and docking
  • Hit clustering and data mining
  • 1D/2D/3D QSAR including COMFA, COMBINE

Center-Driven Project Capabilities

  • Target identification and localization using affinity labeling of probe compounds
  • Yeast three-hybrid systems as tools for identification of protein targets of probe compounds

Biological/Medicinal Chemistry Expertise

  • Analog design
  • Anti-infectives
  • Cancer
  • Cell permeation
  • Central nervous system
  • Natural products chemistry
  • Nuclear receptor system
  • Opioids
  • Proteases

Patrick Faloon, Warren S. Weiner, Daljit S. Matharu, Benjamin Neuenswander, Patrick Porubsky, Willmen Youngsaye, Melissa Bennion, Wai-Leung Ng, Amanda Hurley, Carrie M. Mosher, Stephen Johnston, Sivaraman Dandapani, Frank J. Schoenen, Jeffrey Aubé, Benito Munoz, Michelle Palmer, Bonnie L. Bassler, and Stuart L. Schreiber. “Discovery of ML 370, an inhibitor of Vibrio cholerae Quorum Sensing Acting via the LuxO response regulator.” 2013 Apr 12 [updated 2014 Jan 13]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK189926/ PMID: 24624467

Frank J. Schoenen, Warren S. Weiner, Pierre Baillargeon, Christopher L. Brown, Peter Chase, Jill Ferguson, Virneliz Fernandez-Vega, Partha Ghosh, Peter Hodder, Jeffrey P. Krise, Daljit S. Matharu, Benjamin Neuenswander, Patrick Porubsky, Steven Rogers, Tina Skinner-Adams, Melinda Sosa, Timothy Spicer, Joyce To, Nichole A. Tower, Katharine R. Trenholme, Jenna Wang, David Whipple, Jeffrey Aubé, Hugh Rosen, E. Lucile White, John P. Dalton, and Donald L. Gardiner. “Inhibitors of the Plasmodium falciparum M18 Aspartyl Aminopeptidase.” 2013 Apr 15. [updated 2013 Nov 14]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK179825/ PMID  24479194

Beiyan Zou, Daniel P. Flaherty, Denise S. Simpson, Brooks E. Maki, Melissa R. Miller, Jie Shi, Meng Wu, Owen B. McManus,Jennifer E. Golden, Jeffrey Aubé, and Min Li. “ML365: Development of Bis-Amides as Selective Inhibitors of the KCNK3/TASK1 Two Pore Potassium Channel.” 2013 Apr 15 [updated 2013 Nov 14]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK179826/ PMID 24479195

Donghoon Chung, Chad E. Schroeder, Julie Sotsky, Tuanli Yao, Sudeshna Roy, Robert A. Smith, Nichole A. Tower, James W. Noah, Sara McKellip, Melinda Sosa, Lynn Rasmussen, E. Lucile White, Jeffrey Aubé, and Jennifer E. Golden. “ML336: Development of Quinazolinone-Based Inhibitors Against Venezuelan Equine Encephalitis Virus (VEEV).” 2012 Dec 17 [updated 2013 Nov 7]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK179829/ PMID  24479198

Noah, J. W.; Ananthan, S.; Evans, C. W.; Nebane, N. M.; Rasmussen, L.; Sosa, M.; Tower, N. A.; White, E. L.; Seed, P.; Goller, C.; Arshad, M.; Datta, A.; Neuenswander, B.; Porubsky, P.; Maki, B. E.; Liu, C.; Rogers, S. A.; Schoenen, F.; Aubé, J. "N-(pyridin-4-yl)benzo[d]thiazole-6-carboxamide inhibits E. coli UT189 bacterial capsule biogenesis." 2012 Dec 17 [updated 2013 Apr 5]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK148500/ PMID: 23833802.

Faloon, P. W.; Bennion, M.; Weiner, W. S.; Smith, R. A.; Wurst, J.; Weiwer, M.; Hartland, C.; Mosher, C. M.; Johnston, S.; Porubsky, P.; Neuenswander, B.; Dandapani, S.; Munoz, B.; Schoenen, F. J.; Metkar, S.; Haq, R.; Fisher, D. E.; Aubé, J.; Palmer, M; Schreiber, S. L. "A Small Molecule Inhibitor of the MITF Molecular Pathway." 2012 Dec 13 [updated 2013 Apr 5]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK154496/ PMID: 24027801.

Miller, M. R.; Zou, B.; Shi, J.; Flaherty, D. P.; Simpson, D. S.; Yao, T.; Maki, B. E.; Day, V. W.; Douglas, J. T.; Wu, M.; McManus, O. B.; Golden, J. E.; Aubé, J.; Li, M. "Development of a Selective Chemical Inhibitor for the Two-Pore Potassium Channel, KCNK9." 2012 Apr 16 [updated 2013 Feb 28]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK133427/ PMID: 23658958.

Noah, J. W.; Ananthan, S.; Evans, C. W.; Nebane, N. M.; Rasmussen, L.; Sosa, M.; Tower, N. A.; White, E. L.; Seed, P.; Goller, C.; Datta, A.; Neuenswander, B.; Porubsky, P.; Maki, B. E.; Rogers, S. A.; Schoenen, F.; Aubé, J. "3-(2,6-difluorobenzamido)-5-(4-ethoxyphenyl) thiophene-2-carboxylic acid inhibits E.coli UT189 bacterial capsule biogenesis." 2012 Apr 16 [updated 2013 Mar 14]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK143534/ PMID: 23762949.

Coombs, T. C.; Tanega, C.; Shen, M.; Neuenswander, B.; Porubsky, P.; Wang, J. L.; Misteli, T.; Auld, D. S.; Schoenen, F.; Thomas, C. J.; Aubé, J." Identification of selective inhibitors of cdc2-like kinases 1 and 4 (Clk1, Clk4)." 2012 Apr 16 [updated 2013 May 8]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From: http://www.ncbi.nlm.nih.gov/books/NBK153503/ PMID: 23926621.

Flaherty, D. P.; Golden, J. E.; Liu, C.; Hedrick, M.; Gosalia, P.; Li, Y.; Milewski, M.; Sugarman, E.; Suyama, E.; Nguyen, K.; Vasile, S.; Salaniwal, S.; Stonich, D.; Su, Y.; Mangravita-Novo, A.; Vicchiarelli, M.; Smith, L. H.; Diwan, J.; Chung, T. D. Y.; Pinkerton, A. B.; Aubé, J.; Miller, J. R.; Garshott, D. M.; Callaghan, M. U.; Fribley, A. M.; Kaufman, R. J." Selective small molecule activator of the apoptotic arm of the UPR." 2012 Apr 01 [updated 2013 Feb 28]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK133431/ PMID: 23658962.

Rogers, S.; Patnaik, S.; Schoenen, F.; Zheng, W.; Choi, J.; Motabar, O.; Southall, N.; Westbroek, W.; Goldin, E.; Sidransky, E.; Leister, W.; Marugan, J. J.; Aubé, J. "Discovery, SAR, and Biological Evaluation of Non-inhibitory Chaperones of Glucocerebrosidase." 2012 Mar 27 [updated 2013 Mar 7]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK143537/ PMID: 23762943.

Hong, L.; Simons, P.; Waller, A.; Strouse, J.; Surviladze, Z.; Ursu, O.; Bologa, C.; Gouveia, K.; Agola, J. O.; BasuRay, S.; Wandinger-Ness, A.; Sklar, L.; Simpson, D. S.; Schroeder, C. E.; Golden, J. E.; Aubé, J. "A small molecule pan-inhibitor of Ras-superfamily GTPases with high efficacy towards Rab7." 2011 Dec 16 [updated 2013 Mar 7]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK143553/ PMID: 23762935.

Li, K.; Frankowski, K. J.; Hanson, A. M.; Ndjomou, J.; Shanahan, M. A.; Mukherjee, S.; Kolli, R.; Shadrick, W. R.; Sweeney, N. L.; Belon, C. A.; Neuenswander, B.; Ferguson, J.; Aubé, J.; Schoenen, F. J.; Blagg, B. S. J.; Frick, D. N. "Hepatitis C Virus NS3 Helicase Inhibitor Discovery." 2011 Dec 16 [updated 2013 Mar 14]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK143540/ PMID: 23762946.

Noah, J. W.; Severson, W. E.; Chung, D. H.; Moore, B.; Jia, F.; Xu, X.; Maddox, C.; Rasmussen, L.; Sosa, M. I.; Tower, N. A.; Ananthan, S.; Evans, C. W.; White, E. L.; Jonsson, C.; Matharu, D. S.; Flaherty, D. P.; Simpson, D. S.; Golden, J. E.; Aubé, J. "Identification of a Series of Quinazolinediones as Potent, Selective, Post-Entry Inhibitors of Human Respiratory Syncytial Virus (hRSV) via a Cell-Based High Throughput Screen and Chemical Optimization." 2011 Dec 16 [updated 2013 Feb 28]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK133445/ PMID: 23658939.

Frankowski, K.; Patnaik, S.; Schoenen, F.; Huang, S.; Norton, J.; Wang, C.; Titus, S.; Ferrer, M.; Zheng, W.; Southall, N.; Day, V. W.; Aubé, J.; Marugan, J. J. "Discovery and Development of Small Molecules That Reduce PNC Prevalence." 2011 Nov 15 [updated 2013 Jul 24]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK143533/ PMID: 23762948.

Chen, J.; Young, S. M.; Allen, C.; Waller, A.; Ursu, O.; Strouse, J. J.; Yao, T.; Golden, J. E.; Peterson, B. R.; Foutz, T. D.; Chavez, S. E.; Perez, D.; Evangelisti, A. M.; Garcia, M. J.; Bologa, C. G.; Carter, M. B.; Salas, V. M.; Oprea, T. I.; Edwards, B. S.; Panchaud, N.; De Virgilio, C.; Seeber, A.; Loewith, R.; Manzanilla, E.; Werner-Washburne, M.; Aubé, J.; Sklar, L. A. "Profiling a Selective Probe for RTG Branch of Yeast TORC1 Signaling Pathway." 2011 Apr 15 [updated 2013 Feb 25]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK133439/ PMID: 23658946.

Noah, J. W.; Severson, W.; Chung, D. H.; Moore, B.; Jia, F.; Xu, X.; Maddox, C.; Rasmussen, L.; Sosa, M. I.; Tower, N. A.; Ananthan, S.; White, E. L.; Jonsson, C.; Matharu, D. S.; Golden, J. E.; Prisinzano, T. E.; Aubé, J. "A Cell Based HTS Approach for the Discovery of New Inhibitors of RSV." 2011 Apr 15 [updated 2013 Feb 28]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK133442/ PMID: 23658949.

White, E. L.; Maddox, C.; Nebane, N. M.; Tower, N. A.; McKellip, S.; Manuvakhova, A.; Reddy, L.; Sosa, M.; Rasmussen, L.; Whig, K.; Ananthan, S.; Lun, S.; Bishai, W.; Weiner, W. S.; Schoenen, F.; Dutta, A.; Aubé, J. "Discovery and Development of Highly Potent Inhibitors of Mycobacterium tuberculosis Growth In Vitro." 2011 Apr 15 [updated 2013 Mar 7]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK143189/ PMID: 23762923.

Chou, T. F.; Li, K.; Nordin, B. E.; Porubsky, P.; Frankowski, K.; Patricelli, M. P.; Aubé, J.; Schoenen, F. J.; Deshaies, R. "Selective, reversible inhibitors of the AAA ATPase p97." 2011 Apr 14 [updated 2013 May 01]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK133422/ PMID: 23658965.

Sharlow, E.; Golden, J. E.; Dodson, H.; Morris, M.; Hesser, M.; Lyda, T.; Leimgruber, S.; Schroeder, C. E.; Flaherty, D. P.; Weiner, W. S.; Simpson, D.; Lazo, J. S.; Aubé, J.; Morris, J. C. "Identification of Inhibitors of Trypanosoma brucei Hexokinases." 2010 Dec 15 [updated 2011 Jun 24]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK63599/ PMID: 21961120.

Strouse, J. J.; Ivnitski-Steele, I.; Njus, H. M.; Foutz, T. D.; Yao, T.; Weiner, W. S.; Schroeder, C. E.; Simpson, D. S.; Maki, B. E.; Li, K.; Golden, J. E.; Waller, A.; Evangelisti, A. M.; Young, S. M.; Perez, D.; Chavez, S. E.; Garcia, M. J.; Ursu, O.; Fara, D. C.; Bologa, C. G.; Carter, M. B.; Salas, V. M.; Tegos, G. P.; Oprea, T. I.; Edwards, B. S.; Larson, R. S.; Aubé, J.; Sklar, L. A. "Selective Efflux Inhibition of ATP-binding Cassette Sub-family G Member 2." 2010 Nov 30 [updated 2013 Feb 25]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK133425/ PMID: 23658968.

Hedrick, M. P.; Gosalia, P.; Li, K.; Frankowski, K. J.; Shi, S.; Prisinzano, T. E.; Schoenen, F.; Aubé, J.; Su, Y.; Stonich, D.; Vasile, S.; Sergienko, E.; Gray, W.; Hariharan, S.; Milan, L.; Heynen-Genel, S.; Vicchiarelli, M.; Mangravita-Novo, A.; Streicher, J. M.; Smith, L. H.; Chung, T. D. Y.; Caron, M.; Bohn, L. M.; Barak, L. S. "Antagonist for the Kappa Opioid Receptor." 2010 Oct 31 [updated 2011 May 26]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK66151/ PubMed PMID: 22091479.

Hedrick, M. P.; Gosalia, P.; Frankowski, K.; Shi, S.; Prisinzano, T. E.; Schoenen, F.; Aubé, J.; Su, Y.; Vasile, S.; Sergienko, E.; Gray, W.; Hariharan, S.; Ghosh, P.; Milan, L.; Heynen-Genel, S.; Chung, T. D. Y.; Dad, S.; Caron, M.; Bohn, L. M.; Barak, L. S. "Selective KOP Receptor Agonists: Probe 1 & Probe 2." 2010 Feb 28 [updated 2010 Oct 4]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK50694/ PMID: 21433386.

Hedrick, M. P.; Gosalia, P.; Frankowski, K.; Whipple, D. A.; Shi, S.; Prisinzano, T. E.; Schoenen, F.; Aubé, J.; Su, Y.; Vasile, S.; Sergienko, E.; Gray, W.; Hariharan, S.; Milan, L.; Heynen-Genel, S.; Chung, T. D. Y.; Dad, S.; Caron, M.; Bohn, L. M.; Barak, L. S. "Selective KOP Receptor Antagonists: Probe 1." 2010 Feb 28 [updated 2010 Oct 4]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK50689/ PMID: 21433381.

Surviladze, Z.; Waller, A.; Strouse, J. J.; Bologa, C.; Ursu, O.; Salas, V.; Parkinson, J. F.; Phillips, G. K.; Romero, E.; Wandinger-Ness, A.; Sklar, L. A.; Schroeder, C.; Simpson, D.; Nöth, J.; Wang, J.; Golden, J.; Aubé, J. "A Potent and Selective Inhibitor of Cdc42 GTPase." 2010 Feb 27 [updated 2010 Dec 16]. Probe Reports from the NIH Molecular Libraries Program [Internet]. Bethesda (MD): National Center for Biotechnology Information (US); 2010-. Available From http://www.ncbi.nlm.nih.gov/books/NBK51965/ PMID: 21433396.

People

  • Jeffrey Aubé, Director/Principal Investigator 
  • Brian Blagg, Co-Principal Investigator
  • Frank Schoenen, Project Manager/Associate Director
  • Jennifer Golden&, Assistant Director
  • Shelley Sandberg, Program Manager from 2014 to 2015
  • Cady Bush, Program Manager from 2009 to 2014

Chemistry Team Leaders

  • Brian Blagg, Professor of Medicinal Chemistry
  • Apurba Dutta, Associate Professor of Medicinal Chemistry
  • Jennifer Golden, Associate Research Professor, Higuchi Biosciences Center
  • Blake Peterson, Regents Distinguished Professor of Medicinal Chemistry
  • Thomas Prisinzano, Professor of Medicinal Chemistry
  • Frank Schoenen, Associate Research Professor, Higuchi Biosciences Center

Staff Members

  • Benjamin Neuenswander, Purification Core Leader
  • Patrick Porubsky, Compound Curator
  • David Hill, Lab Manager
  • Daniel Flaherty, Assistant Research Professor
  • Kevin Frankowski, Assistant Research Professor
  • Tuanli Yao, Research Associate
  • Sudeshna Roy, Postdoctoral Research Associate
  • Chad Schroeder, Research Assistant
  • Jun (Luke) Huan, Core Co-Leader
  • Jenna Wang, Research Associate
  • Jared Rudy, Systems Specialist
  • Dale Boger, The Scripps Research Institute
  • Samuel Gerritz, Bristol-Myers Squibb
  • Lester Mitscher, Distinguished Professor, University of Kansas
  • Michael Rafferty, Adjunct Professor, University of Kansas)
  • Christian Schöneich, Distinguished Professor, University of Kansas