SCREENING OF UNIQUE BINDING SITE SPECIFIC LIGAND FOR CARBONIC ANHYDRASE IX

Cancer is a common and widespread cause of human death in the world. Treatments like chemotherapy and radiotherapy facilitate in prolonging the patient’s life however in some cases cancer can be prevented. Cancers like breast, prostate, colon, renal cell carcinoma are caused by the overexpression of an enzyme termed Carbonic Anhydrase IX (CAIX). In 2015, 60,290 new cases of breast cancer alone are estimated. If this overexpression is controlled using an inhibitor, then the mortality rates due to cancer can be brought down by a significant margin.  The primary objective of this research is to find an inhibitor that would reduce or down regulate the overexpression of CAIX in the human body. The inhibitor would specifically target CAIX. CAIX has a region which is unique and its cavities were identified. These were docked with the chosen inhibitor. Numerous acetazolamides and sulfanilamides were tested as inhibitors. Various bioinformatics tools such as Maestro and Hex were used for docking and grid generation.  Docking scores were obtained and studied. The inhibitors with the highest negative docking score was selected. Two cavities were found to be the most efficient. Indane sulphonamide (PDB ID- 2QOA) was found to be the best fit for cavity 2 while Carbonic Anhydrase II Inhibitor (PDB ID- 2X7T) was found to be the best fit for cavity 6. The future in this direction of research is the possible production of anti-cancer drugs, immune therapy, cancer specific antibodies, usage of selective inhibitors and many such novel strategies to battle against cancer.