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Title:Development and Mechanistic Characterization of Novel Small Molecules as Cancer Therapeutics
Author(s):Palchaudhuri, Rahul
Director of Research:Hergenrother, Paul J.
Doctoral Committee Chair(s):Hergenrother, Paul J.
Doctoral Committee Member(s):Mitchell, Douglas A.; Shapiro, David J.; Baranger, Anne M.
Department / Program:Chemistry
Discipline:Chemistry
Degree Granting Institution:University of Illinois at Urbana-Champaign
Degree:Ph.D.
Genre:Dissertation
Subject(s):Cancer
Therapeutic
Mechanism of action
Small Molecule
Abstract:The discovery and development of novel small molecules as anti-cancer agents plays an integral role in the fight against cancer. Such efforts will lead to the development of the therapies of tomorrow. Potentially useful molecules may be discovered through cell-based toxicity screens, enzyme-based in vitro screens or developed from computational design against proteins of interest. The elucidation of the mechanism of action of small molecules discovered in cell-based screens remains a challenging endeavor. Whole genome transcript profiling and genome-wide shRNA screens are tools that have recently become available to the researcher and their use in aiding mechanism elucidation is reviewed in Chapter 1. Also presented herein is the development and investigation of the mechanism of action of several novel small molecules that exhibit anti-cancer activity. Genome-wide technologies are employed to characterize the mechanism of several of these molecules. Chapter 2 focuses on the mechanism of a rapid inducer of caspase-dependent apoptosis. Chapters 3 and 4 investigate novel triphenylmethyl containing anticancer agents and compare their mechanisms of action to known agents. The development of lactate dehydrogenase-A (LDH-A) inhibitors as a novel anticancer strategy is discussed in Chapter 5. In Chapter 6, the mode of action of anti-cancer quinones is described. And finally, the discovery of triazole-containing small molecules as tubulin-targeting agents is narrated in Chapter 7.
Issue Date:2011-08-26
URI:http://hdl.handle.net/2142/26382
Rights Information:Copyright 2011 Rahul Palchaudhuri
Date Available in IDEALS:2011-08-26
2013-08-27
Date Deposited:2011-08


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