G-Quadruplex-Interactive Compounds as Possible Anticancer Agents

Introduction

There have been few dramatic therapeutic breakthroughs in cancer research. Many more anticancer drugs are in use today than ever before, but nearly all of these drugs are severely limited in their use due to the dual problems of drug resistance and lack of selectivity. With cancer becoming more and more common, the need for cancer detection has become more important. Few techniques are available, and very few detect it early.

Invention Description

This technology has a variety of methods for screening libraries of compounds for G-quadruplex interactive agents. These methods are both computational and biochemical, allowing the screening of real as well as virtual libraries. Using these methods, we have discovered a number of classes of novel G-quadruplex interactive compounds. These compounds are inhibitors of the cancer-cell specific enzyme telomerase, and have potential as anticancer agents. Considerable evidence suggests that these structures can exist in vivo in specific regions of the genome including the telomeric ends of chromosomes and oncogene regulatory regions. Recent studies have demonstrated that small molecules can facilitate the formation of, and stabilize, G-quadruplexes. Certain sequences of DNA are able to form unique G quadruplex structures. These structures are implicated in a variety of biological processes. One example of such a process is the cancer-cell specific elongation of chromosome telomeres by the enzyme telomerase. G quadruplex structures have also been implicated in the transcriptional control of specific genes, and in inherited diseases such as fragile X syndrome.

Benefits

• These pro-drugs are readily taken up by lung cancer cells.
• Importantly, these compounds do not interfere with other essential DNA processing enzymes present in normal cells.
• High selectivity allows exposure of cells and animals to compounds without toxicity concerns.

Features

• Anticancer drug discovery
• High-throughput screening
• Gene-specific transcriptional control
• Compound displays the ability to fool telomerase and to be incorporated into the telomere DNA

Market Potential/Applications

Cancer is the second leading cause of death in the United States. Each year over half a million Americans die from cancer. The global cancer market is predicted to be worth around $20 billion in 2004, and is expected to increase to over $45 billion by 2011. Over the next decade, advances in the pharmacotherapy of cancer will come not only from improvements in the traditional classes of therapies, but also from introduction of inno vative therapies such as this one, that display improved efficacy and toxicity through a targeted approach.

Development Stage

Proof of concept completed.

IP Status

U.S. Patent Issued: 6,156,763
U.S. Patent Issued: 6,623,930
U.S. Patent Issued: 6,689,887
3 Foreign Applications pending One PCT Application filed

UT Researcher

Sean Kerwin, Ph.D., College of Pharmacy, The University of Texas at Austin

For further information please contact:

University of Texas,
Austin, USA
Website : www.otc.utexas.edu