In 2020 an estimated 1,806,590 cases of cancer were diagnosed in the United States alone, and 606,520 people have died from this disease. Fatty acid synthase (FASN) is a very important enzyme that is involved in cancer biology. Fatty acid synthase is the only known enzyme that can catalyze synthesis of palmitate, which is vital because cancer cells become dependent on palmitate for several different processes. Accumulating evidence suggests that fatty acid synthase is a metabolic oncogene with a vital role in the growth and survival of tumors. For instance, patients whose tumors contain little to no FAS have a 52% greater chance of being alive after two years than those whose tumors contain abundant amounts of FASN. In order to learn more about the FASN we will design our inhibitors using a computer-modeling software called AutoDockTools. We will prepare the crystallographic protein and then screen commercially available compounds for binding into the active site of FASN. After the screening is complete, we will analyze the compounds by examining where they bind on the protein, how they bind, and what types of interactions they make with the protein. In addition, we will perform a structure-activity relationship study by examining similar compounds and comparing and contrasting the binding modes and docking scores. In the end, we will identify a few compounds that score high on the above properties as candidates for chemical synthesis. Lastly, we will synthesize one of these target FASN1 inhibitors and these results will be presented.

Structure guided design and synthesis of fatty acid synthase inhibitors for the treatment of cancer

ACS Spring 2022

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