American Family Children's Hospital

Scientific Accomplishments

Computational Modeling and Docking


James Keck, PhD - Cell Signaling Program
NIH R01 GM068061

  • CFAM (2-[2-chloro-5-(trifluoromethyl)anilino]-5-methoxybenzoic acid) identified in HTS at Small Molecule Screening Facility (SMSF) by disruption of protein interaction involved in genome maintenance.
  • CFAM co-crystalized with target Exonuclease I (in black in Figure).
  • In-silico docking of 400,000 compound database identified compounds (in gold in Figure) for CFAM binding site that are currently being tested for improved potency and selectivity.

Scientific Accomplishment #1

Lu D, Bernstein DA, Satyshur KA, Keck JL. Small-molecule tools for dissecting the roles of SSB/protein interactions in genome maintenance. Proc Natl Acad Sci USA, 2010 Jan 12;107(2):633-8. PMID:20018747.





PI: George Wilding, MD - Experimental Therapeutics Program

Study Chair: William Schelman, MD, PhD - Experimental Therapeutics Program 

NCI U01 CA062491

  • UWCCC 3P Laboratory needed [13C]6-bortezomib as an internal standard to develop a method to detect plasma concentrations of bortezomib for a Phase I study of Suberoyalanilide Hydroxamic Acid (SAHA) in Combination with Bortezomib in Patients with Advanced Malignancies.
  • SMSF synthesized and purified 13C-labeled bortezomib.
  • 3P successfully developed the method.

Scientific Accomplishments #2






David Jarard, MD - Cell Signaling Program

NCI R01 CA97131 

  • Induction of senescence may be useful for cancer treatment.1
  • HTS at SMSF identified compounds that induce senescence from a 4160 compound library (Figure).
  • Candidate compounds selected based on secondary assays for persistent growth arrest after drug removal and increased expression of previously described senescence marker genes.
  • Four compounds not previously associated with senescence identified for further investigation (diazequone, bithionol, dichlorophene, pyrithione)2

Scientific Accomplishments #3


1Ewald JA, Desotelle JA, Wilding G, and Jarrard DF. Therapy-induced senescence in cancer. J Natl Cancer Inst, 2010;102(20):1536-46.

2Ewald JA, Peters N, Desotell, JA, Hoffman, FM, and Jarrard DF. A high-throughput method to identify novel senescence-inducing compounds. J Biomol Screen, 2009; 14(7):853-8.



siRNA Screening


Mark Burkard, MD, PhD - Cell Signaling Program

Mary Kay Ash Charitable Foundation Grant 013-10

  • Cancers harbor supernumerary chromosomes (polyploidy) that could provide a 'targetable' abnormality.
  • Derived matched diploid and tetraploid cell lines and performed a synthetic lethal siRNA screen of over 2000 targets.
  • A small number of siRNAs reduced 4N proliferation without affecting 2N proliferation (red box in Figure), including siRNAs to a number of potassium channels.
  • Potassium channel inhibitors might provide synthetic lethal effects on 4N cells and not on 2N cells and may make suitable therapeutics for polyploid cancers.

Scientific Accomplishments #4