Development and Mechanistic Characterization of Novel Small Molecules as Cancer Therapeutics

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2011

Author dc:creator

• Palchaudhuri, Rahul

Contributors dc:contributor

• Hergenrother, Paul J.
• Mitchell, Douglas A.
• Shapiro, David J.
• Baranger, Anne M.

• Cancer
• Therapeutic
• Mechanism of action
• Small Molecule

Statement dc:rights

• Copyright 2011 Rahul Palchaudhuri

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/26382

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/26382