IPA was used to identify mechanism of action of small molecule compounds.
PLoS ONE 5(10): e13131. Published: October 4, 2010. Melissa Millard, Divya Pathania, Yumna Shabaik, Laleh Taheri, Jinxia Deng, Nouri Neamati
"We performed protein microarray to better understand the mechanism of action of phosphonium salts recently discovered in our laboratory. The IPA platform was an invaluable tool, allowing us to quickly and efficiently organize and analyze the large amount of data provided by microarray. In addition, by using the pathway designer tools, we were able to create attractive and informative figures to illustrate the signaling pathways most significantly affected by our compounds."
Dr. Melissa Millard, Ph.D. candidate
University of Southern California (USC) School of Pharmacy
Department of Pharmacology and Pharmaceutical Sciences
Melissa Millard and the USC team utilized IPA to understand how small-molecule compounds target cancer-cell metabolism, primarily through the mitochondria. IPA helped the team visualize protein-protein networks, relationships, functions, pathways, and mechanisms which ultimately helped to understand the mechanism of action of the small-molecule compounds. IPA enabled the team to statistically rank 70 pathways in order of significance, where the top-ranked pathway was the Hepatocyte Growth Factor signaling pathway, a likely target of TP421 treatment. This pathway is important because it signals to numerous downstream effectors that mediate cell survival, death, adhesion and motility, and progression through the cell cycle. The significantly up-regulated or down-regulated proteins were analyzed by IPA Core Analysis to analyze TP421-mediated signally pathways.
Melissa Millard (a Ph.D. candidate at USC’s School of Pharmacy) recently presented a poster titled "Preclinical Evaluation of Novel Triphenylphosphonium Salts With Broad-Spectrum Activity" at the
American Association for Cancer Research (AACR) in Orlando, Florida in April 2011. Their results are also published in the October 2010 issue of PLoS ONE. Additional authors include Divya Pathania, Yumna Shabaik, Laleh Taheri, Jinxia Deng and Nouri Neamati. |
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