Novel Anticancer Pro-Drugs Activated by Hydrogen Peroxide
- Technology Benefits
- Safer – Prodrugs are specifically designed only to be toxic for cancer cellsSpecific activation – Targeted specifically to the tumor microenvironment Versatile – The triggers can be added to a wide variety of already known cancer drugs Multifunctional – The compounds contain multiple effectors for fighting cancer cells Better drug properties – Prodrug design can aid in pharmaceutical problems of poor solubility, poorchemical stability, insufficient absorption, inadequate blood-brain barrier permeability, and presystemicmetabolism
- Technology Application
- In the last decade, oncology has been one of the largest segments in the pharmaceutical market, with amajor focus on targeted agents specific to tumors. Global oncology spending hit $91 billion last year andis growing at 5% annually. The NIH estimates that the overall costs of cancer in 2010 were approximately$264 billion. Targeted cancer drugs now make up 46% of cancer sales. Cancer is the second mostcommon cause of death in the US, only exceeded by heart disease, accounting for nearly 1 in every 4deaths.
- Detailed Technology Description
- Dr. Xiaohua Peng has used a synergistic combination of synthetic chemistry and biological techniques forthe development of new anticancer agents that target the tumor microenvironment. Specifically, she hasdesigned pro-drug compounds containing “triggers” that are activated by high levels of hydrogen peroxidedeep inside a tumor.
- Application No.
- Non-Confidential Summary
- *Abstract
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The compounds contain multiple potent effectors, some of which have beendesigned to cause DNA damage within the tumor leading to cell death. Several of these compoundshave undergone initial testing through the National Cancer Institute’s NCI 60-Cell Line Screen, and showpromise in causing cell growth inhibition or death in Leukemia, Non-Small Cell Lung Cancer, and breastcancer. In vitro cytotoxicity assays with H2O2 inducible compounds have shown growth inhibition ofcancer cells at less than 1 micromolar and they induced apoptosis in primary leukemic lymphocytes. Anude mouse xenograft trial for breast cancer showed significant decreases in tumor size in treated mice.
Cancer therapies are often as toxic tohealthy cells as to cancer cells. A majorfocus in the development of newtherapeutics is to exploit differences incancer cells so that therapies can behighly targeted to avoid unwanted sideeffects. Cancer cells are known to exhibitincreased intrinsic oxidative stress suchas hydrogen peroxide. Dr. Peng’s ROSactivatedtriggers provide a newalternative for clinical use. These prodrugsare designed to undergo tumorspecificactivation to release compoundsthat cause DNA inter-strand cross-links,which are deleterious to cancer cellsbecause they block DNA replication andtranscription. These compounds areideal for cancer treatment due to theirlack of toxicity in the body until they are located within the tumor microenvironment.
- *IP Issue Date
- None
- *IP Type
- Download
- *Principal Investigator
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Name: Sheng Cao
Department:
Name: Yunyan Kuang
Department:
Name: Xiahua Peng, Assistant Professor
Department:
Name: Yibin Wang
Department:
- Country/Region
- USA
