Three UNC-Chapel Hill professors from the Eshelman School of Pharmacy received a patent for a new compound to treat childhood leukemia and other forms of cancer, according to a filing Tuesday with the U.S. Patent and Trademark Office.

Xiaodong Wang, Stephen Frye and Dmitri Kireev, along with three other individuals, filed for the patent in late February 2016.

According to the patent application, acute lymphoblastic leukemia is the most common malignancy in children, and common varieties are cured by chemotherapy in 75 percent to 85 percent of the cases.

However, resistance to and relapse from therapy is a major cause of pediatric cancer death. In addition, all chemotherapies can cause complications that are increasingly recognized in pediatric survivor populations.

Bio: Xiaodong Wang, Ph.D.

Director of Medicinal Chemistry, chemistry, CICBD research associate professor

Research:

  • Drug Discovery

The majority of cellular pathways, especially those involved in signal transduction, are regulated by kinases. Kinases are proteins that can modify other proteins by phosphorylation at one of three amino acids that have a free hydroxyl group. Phorsphorylation results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. Inappropriate kinase expression and activity is a frequent cause of disease, in particular cancer. Small molecule inhibitors have been introduced into the clinic for treatment of certain cancers. We are currently focused on developing small molecule Mer inhibitors as clinical candidates to treat pediatric acute lymphoblastic leukemia. We are also interested in other kinases such as IKKepsilon/TBK1 and ROR2.

  • Synthetic Methodology Development

Heterocyclic compounds are widely used in drug discovery as synthetic pharmacophores. However, some are not readily available and are difficult to prepare in the variety and quantities needed for structure-activity relationship studies. We are currently interested in developing short, effective and robust synthetic routes to prepare heterocycles such as pyrazolopyrimidines and pyrrolopyrimidines.

Source: UNC

Wang, who directs medicinal chemistry at the Eshelman School of Pharmacy, is listed as the first inventor on the patent. She is currently focused on developing small molecule inhibitors as clinical candidates to treat pediatric acute lymphoblastic leukemia.

Frye is a professor and director of the Center for Integrative Chemical Biology and Drug Discovery. Frye is also the lead principal investigator for the North Carolina Comprehensive Chemical Biology Center, a UNC-based center that engages in oncology drug discovery.

Kireev is a research professor and director of computational biophysics and molecular design, which develops and applies computational tools to advance the understanding of complex biological systems and discover therapies for unmet medical needs.

Patent overview: Fighting leukemia

  • FIELD OF THE INVENTION

The present invention concerns compounds, compositions and methods for the treatment of cancer.

  • BACKGROUND OF THE INVENTION

Acute Lymphoblastic Leukemia (ALL) is the most common malignancy in children and common varieties are cured by chemotherapy in 75%-85% of the cases. Collectively the less common T cell and rare B cell subsets represent less than 2000 cases yearly and thus can be classified as a rare disease; these subsets have a poorer prognosis. Unfortunately with either subset, resistance to and relapse from therapy is a major cause of pediatric cancer death. In addition, ALL chemotherapies can cause late complications that are increasingly recognized in pediatric survivor populations. In fact, in pediatric cancer survivors, the incidence of severe late effects (neurocognitive sequelae, auditory complications, cardiovascular dysfunction, gastrointestinal/hepatic dysfunction, growth delay, secondary malignancies, and infertility) directly related to therapy is approximately 25%. A better understanding of therapeutic resistance and its reversal could not only help those who relapse but may help lower the dose of chemotherapy needed in ALL patients thus reducing long-term toxicity for future survivors.

  • SUMMARY OF THE INVENTION

The ectopic expression of Mer receptor tyrosine kinase (Mer) has been identified as a tumor cell survival gene product in Acute Lymphoblastic Leukemia (ALL) cells and a potential cause of ALL chemoresistance. Hence, we investigated whether the development of small molecule Mer inhibitors was possible.

Read full patent at:

http://patft.uspto.gov/netacgi/nph-Parser?Sect2=PTO1&Sect2=HITOFF&p=1&u=/netahtml/PTO/search-bool.html&r=1&f=G&l=50&d=PALL&RefSrch=yes&Query=PN/9744172

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