chemistry seminar - st. cloud state university · chemistry seminar dr. venkatram mereddy...
TRANSCRIPT
MONDAY, SEPT. 12, 2016
12:00 P.M.
WSB-122
SEMINAR CHEMISTRY
DR. VENKATRAM MEREDDY DEPARTMENT OF PHARMACY PRACTICE & PHARMACEUTICAL SCIENCES
U. OF MINNESOTA, DULUTH
"SIMPLE ORGANIC CHEMISTRY SOLUTIONS TO
COMPLEX CANCER PROBLEMS"
Abstract: Advances in cancer treatment with chemotherapy have been successful in reducing cancer-related deaths over the past 50 years. However, many of these cancer drugs have harsh side effects and become ineffective when a tumor becomes resistant to a drug, leading to treatment failure and patient mortality. Therefore, new candidate compounds that have the ability to treat a wide variety of cancer types, have low side effects, and are successful in treating advanced stage and drug-resistant tumors are urgently needed. One fundamental difference between cancer cells and normal cells of the body, is the way in which they generate energy. Cancer cells are unique in that they primarily use glycolysis to generate energy, a process which normal cells only use sparingly. In this regard, our lab use small organic molecules to target tumor glycolysis via inhibition of monocarboxylate transporters (MCTs). MCTs are over expressed in many breast cancer cell lines, and hence their inhibition has tremendous clinical potential. As the grade of the cancer worsens, it adopts an aggressive glycolytic process for energy production. The number of MCTs on the cell surface increases proportionately to efflux/influx the resulting lactate and this fact is very important in opening other possibilities for treatments of relapsed and metastasized cancers. Over the past five years we have created novel small molecule MCT inhibitors and synthesized and evaluated more than 300 new compounds. Of these we have discovered several aqueous soluble and potent MCT1/4 dual inhibitors that are active at low nM concentrations. Anticancer efficacy studies in mice bearing breast cancer tumor xenograft, colorectal and also aggressive glioblastoma models have shown that these drugs efficiently reduce tumor burden without causing any systemic toxic side effects.