Navigation Links
U-M researchers ID promising new cancer drug

ANN ARBOR, Mich. Researchers have long searched for a novel cancer drug that activates a certain protein to kill tumor cells. But finding a drug that kills the cancer without causing damage to normal cells has stymied researchers.

Now, researchers at the University of Michigan Comprehensive Cancer Center have designed a small molecule that is highly effective in cell cultures at inhibiting the interaction between this protein, called p53, and another protein that inactivates p53 in cancer. The new molecule is ideal for drug development as it can be given orally as a pill and it appears to be safe for use in animals.

For more than 10 years scientists have searched for ways to block p53 inhibition, but with little success. Our study clearly shows that this can be done, says study author Shaomeng Wang, Ph.D., Warner-Lambert/Parke-Davis Professor in Medicine at the U-M Medical School and co-director of the molecular therapeutics program at the U-M Comprehensive Cancer Center.

If clinical trials prove out the drugs promise, it could have potential for treating many different types of cancer. Results of the study appear the week of March 3 in the online edition of the Proceedings of the National Academy of Sciences.

The protein p53, which normally helps suppress tumors, is inactivated in almost all human cancers. About half the time, p53 does not do its job because the gene that holds the protein is mutated or missing altogether. The other half of the time, another protein, called human MDM2, is the culprit. It binds to p53 and inhibits the tumor suppressor function of p53, promoting cancer development.

Using a computer-assisted approach, U-M researchers designed a small molecule, called MI-219, that is highly effective in blocking the interaction of MDM2 and p53. MI-219 specifically kills tumor cells by harnessing the power of p53. In animal models of human cancer, MI-219 completely inhibited tumor growth and appeared to cause no toxicity to animals.

Many traditional cancer drugs also activate p53 but they do so by causing DNA damage. They kill not only tumor cells but also normal cells, thus having severe side effects. MI-219 is unique in that it is designed to activate p53 without causing DNA damage, specifically killing tumor cells. Indeed, MI-219 is highly effective in inhibiting tumor growth, and even inducing tumor regression, but it has caused no toxicity to animals at efficacious doses, says Wang, professor of internal medicine and pharmacology at the U-M Medical School and professor of medicinal chemistry at the U-M College of Pharmacy.

In addition to its effectiveness at killing cancer cells without toxic side effects, MI-219 can be developed as a pill that patients could take orally, rather than the traditional chemotherapy drugs that must be given intravenously at a hospital or cancer center.

While promising in preclinical studies, MI-219 needs to be evaluated in human clinical trials for its safety and efficacy for cancer treatment since it is a brand new drug, Wang cautions.

"We are very excited about the therapeutic potential of MI-219 for the treatment of many types of human cancer. Ascenta is committed to advancing MI-219, which we have designated AT-219, into human clinical trials," says study author Dajun Yang, M.D., Ph.D., senior vice president of research and a co-founder of Ascenta Therapeutics, a clinical-stage biopharmaceutical company that has licensed the technology related to MI-219 from U-M and plans to aggressively advance it into human clinical trials.


Contact: Nicole Fawcett
University of Michigan Health System

Related medicine news :

1. Researchers identify new genetic marker for breast cancer
2. Researchers describe mechanisms by which capon gene causes heart rhythm disturbances
3. Researchers develop new tool to predict who will use microbicides
4. USC researchers discover novel way to develop tumor vaccines
5. St. Jude Researchers Find Key Step in Programmed Cell Death
6. St. Jude researchers find key step in programmed cell death
7. Mayo Researchers Look for Explanation Behind High Incidence of Diabetes Among Asian Indians
8. Mayo researchers look for explanation behind high incidence of diabetes among Asian Indians
9. UT Southwestern researchers investigate predictors for sickle-cell-anemia complications
10. Researchers find possible target to treat deadly bloodstream infections
11. Rutgers researchers unlock mysteries of vitamin A metabolism during embryonic development
Post Your Comments:
Related Image:
U-M researchers ID promising new cancer drug
(Date:6/25/2016)... ... 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe earned his ... David Geffen School of Medicine at UCLA. He trained in Internal Medicine at Scripps ... in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the opportunity to ...
(Date:6/25/2016)... ... June 25, 2016 , ... On Friday, June 10, Van Mitchell, Secretary of ... award to iHire in recognition of their exemplary accomplishments in worksite health promotion. , ... Workplace Health & Wellness Symposium at the BWI Marriott in Linthicum Heights. iHire was ...
(Date:6/24/2016)... ... 24, 2016 , ... A recent article published June 14 on ... article goes on to state that individuals are now more comfortable seeking to undergo ... such as calf and cheek reduction. The Los Angeles area medical group, Beverly Hills ...
(Date:6/24/2016)... ... June 24, 2016 , ... June 19, 2016 is World Sickle Cell Observance ... and the benefits of holistic treatments, Serenity Recovery Center of Marne, Michigan, ... Disease. , Sickle Cell Disease (SCD) is a disorder of the red blood cells, ...
(Date:6/24/2016)... (PRWEB) , ... June 24, 2016 , ... ... Conference and Scientific Sessions in Dallas that it will receive two significant new ... the grants came as PHA marked its 25th anniversary by recognizing patients, medical ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... June 23, 2016 Any dentist who has made ... the current process. Many of them do not even offer ... difficulties and high laboratory costs involved. And those who ARE ... at such a high cost that the majority of today,s ... Dr. Parsa Zadeh , founder of Dental Evolutions Inc. ...
(Date:6/23/2016)... a startling report released today, National Safety Council research ... proven plan to eliminate prescription opioid overdoses. Prescription Nation ... tackling the worst drug crisis in recorded U.S. history, assigned a ... , New Mexico , Tennessee ... failing states, three – Michigan , ...
(Date:6/23/2016)... 2016 Research and Markets has announced ... Analysis 2016 - Forecast to 2022" report to their ... contains up to date financial data derived from varied research ... trends with potential impact on the market during the next ... which comprises of sub markets, regional and country level analysis. ...
Breaking Medicine Technology: