New Compound Is Effective Against Drug-Resistant Leukemia, Pre-clinical Study Finds

ATLANTA (March 17, 2016) – A novel compound has shown promise in preclinical studies as a treatment for acute myeloid leukemia (AML), more than doubling median days of survival even in a drug-resistant form of the disease.

Researchers at the Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta, Emory University School of Medicine, University of Colorado Anschutz Medical Campus, University of North Carolina Lineberger Comprehensive Cancer Center and the University of North Carolina Eshelman School of Pharmacy report that MRX-2843 blocked the growth of AML cells, led to a significant level of cancer cell death and more than doubled the median days of survival in laboratory models with a drug-resistant form of the disease.

Researchers said the findings, which were published today in the journal JCI Insight, could pave the way for human clinical trials.

 “Our data indicate that this could be a superior drug for certain resistant forms of acute myeloid leukemia; however, it has to be tested in clinical trials,” said Shelton Earp, MD, Director of UNC Comprehensive Cancer Care and a Lineberger Professor of Cancer Research. “We know that leukemia can develop resistance to drugs similar to ours. The questions is: Would this new UNC inhibitor give patients with resistant AML longer survival? This is a particularly salient question for older AML patients who can’t tolerate high doses of chemotherapy and bone marrow transplant.”

MRX-2843 was designed to specifically target two cell signaling proteins called tyrosine kinases that help drive abnormal cell growth in AML, non-small cell lung cancer, melanoma and glioblastoma.

Researchers had set out to create a compound that would block MERTK, a protein that the researchers found to be over-expressed in AML cells, but they later determined that the compound could also block the FLT3 protein. FLT3 is mutated in 20-30% of adults and in 10-15% of children with AML and is associated with worse outcomes in patients.

The compound was developed in the UNC Center for Integrative Chemical Biology and Drug Discovery, which is led by Stephen Frye, PhD, a UNC Lineberger faculty member and the Fred Eshelman Distinguished Professor in the UNC Eshelman School of Pharmacy, with funding from the National Cancer Institute (NCI) Experimental Therapeutics Program, or NCI NeXT. Dr. Frye’s group made more than 1,500 compounds targeting MERTK.

“We examined the structure of a small molecule bound at the active site of the MERTK tyrosine kinase enzyme, and then we designed compounds to be more potent or selective,” Dr. Frye said. “Research faculty Xiaodong Wang, PhD, and Dmitri Kireev, PhD, multiple chemists and post-doctoral fellows in my lab contributed to this discovery.”

The MERTK protein itself was originally discovered by Doug Graham, MD, PhD, Director of the Aflac Cancer and Blood Disorders Center and Chief of the Emory University Division of Pediatric Hematology/Oncology/BMT, when he was a graduate and medical student in the Earp lab at UNC Lineberger. After graduating from UNC, Dr. Graham continued researching MERTK in his lab at the Children’s Hospital of Colorado and Children’s Healthcare of Atlanta.

“Our research has shown that when the MERTK protein in a cell is ‘turned on,’ it can give a cancer cell a survival advantage and often make the cancer cell less responsive to traditional chemotherapy drugs,” Dr. Graham said. “We have been working as a team across multiple labs to develop drugs that effectively ‘turn off’ the MERTK protein. The MRX-2843 compound is effective at targeting cancer cells with activated MERTK. With the U.S. Food and Drug Administration’s IND approval to start a first-in-human clinical trial, we hope to bring this drug to adults battling these specific cancers, and ultimately if successful in adults, to the pediatric population.”

In tests using multiple preclinical models, researchers demonstrated that MRX-2842 blocked the growth of AML cells and led to a significant level of cancer cell death. They also determined that giving the compound orally once a day to mice with human AML tissue increased the mice’s survival two to three times.

The drug also remained effective against AML models that developed resistance to another potential drug. In mice with one of two additional FLT3 mutations that drive drug resistance, treatment with MRX-2843 increased survival from 35.5 to 94 days, while another drug in development for AML and mutated FLT3 increased survival from 36 to 45 days.

“We know that mutations arise where other compounds bind in the active site of FLT3 so that they will no longer bind,” Dr. Frye said. “Data from this study show that our compound is still potent against these resistant mutants because ours has a different binding mode.”

Drs. Graham, Frye and Earp are co-founders of the Research Triangle Park-based startup company Meryx Inc. that was launched to support the drug’s development. Meryx has licensed the rights to the drug from UNC and received funding through Carolina KickStart. The university program provides funding to help UNC startups companies with technology validation, product and business development.


For more information:

Allyson Wright

Public Relations, Manager


About The Aflac Cancer and Blood Disorders Center of Children’s

The Aflac Cancer and Blood Disorders Center of Children’s Healthcare of Atlanta is a national leader among childhood cancer, hematology, and blood and marrow transplant programs, serving children and young adults. Recognized as one of the top childhood cancer centers in the country by U.S. News & World Report, the Aflac Cancer and Blood Disorders Center cares for more than 500 newly diagnosed cancer patients and treats nearly 2,000 unique sickle cell disease patients each year. Our program offers patients access to more than 380 clinical trials, including 28 innovative Aflac Cancer and Blood Disorders Center investigator-initiated trials. Visit for more information.

UNC Lineberger

One of only 45 National Cancer Institute (NCI)-designated comprehensive cancer centers, the University of North Carolina Lineberger Comprehensive Cancer Center brings together some of the most exceptional physicians and scientists in the country to investigate and improve the prevention, early detection and treatment of cancer. With research that spans the spectrum from the laboratory to the bedside to the community, UNC Lineberger faculty work to understand the causes of cancer at the genetic and environmental levels, to conduct groundbreaking laboratory research, and to translate findings into pioneering and innovative clinical trials. For more information, visit  


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