IDENTIFICATION OF NATURAL BRAF INHIBITORS AS POTENTIAL ALTERNATIVES TO DABRAFENIB: AN IN SILICO STUDY

Abstract

Melanoma is the most aggressive form of skin cancer that appears to affect a major section of population. It is the sixth most common form of cancer in the United States itself. UV rays are a common mutant which cause the alterations in multiple genes in the melanin producing melanocytes. The mutations in oncogenes along with loss of cell cycle control result in melanoma. This form of cancer has been associated with age as prolonged exposure to UV rays caused oncogenic mutations leading to cancer. But now, due to changing environmental conditions and altered lifestyle and beauty standards, young people and even children are melanoma patients. There are multiple FDA approved drugs and therapies which are used to treat melanoma. Dabrafenib is one such drug which inhibits the mutated BRAF. It has been proved to be useful over the years but due to multiple underlying interactions, there is a general drug resistance and appearance of side effects like hyperglycemia. In this study, computational tools like virtual screening and molecular docking were used to determine multiple off target interactions of Dabrafenib. AKT which is also responsible for glucose management was figured out to be a major reason behind instances of hyperglycemia in Melanoma patients. Also, attempts were made to identify the natural compound which can be used as an alternative for Dabrafenib. All this is done using AutoDock Vina as a molecular docking tool. We were able to identify a natural compound, Gericudranin A which can be potentially used as a safer alternative for Dabrafenib as it has shown comparative interactions with the target and relatively less likeliness to cause Hyperglycemia.