Carbonic Anhydrase IX Inhibitors: Finding Potential Therapeutic Cancer Agents Through Virtual Screening

Authors:  Vanna Hovanky & Keyur Mehta

Cancer is one of the leading causes of death and affects over seven million people each year (American Cancer Society, 2011). Carbonic anhydrase IX (CAIX) is an enzyme that increases the survival of cancer cells and renders treatments ineffective by regulating tumor pH. The purpose of the project was to discover and test novel inhibitors of CAIX that can potentially block tumor growth. A total of 86,228 compounds were virtually screened. The DNA sequence coding for the human carbonic anhydrase IX protein was inserted into a bacte- rial expression vector and expressed and purified via nickel affinity tag. Spectrophotometric enzyme assays measured the effectiveness of the compounds in vitro. Virtual screening results demonstrated that metoprolol, pentamidine isethionate, and Chembridge compounds #7653639 and #7633756 have predicted drug-likeness and binding strength to the CAIX active site through favorable interactions of Van der Waals forces and hydrogen bonds.