Synthesis of Benzimidazoles as K-Ras Inhibitors for Cancer Chemotherapy

The KRAS gene, first identified as an oncogene in the Kirsten RAt Sarcoma virus, provides instruction towards the production of the K-Ras protein. The K-Ras protein is responsible for relaying various growth signals from outside of the cell to the cell’s nucleus. When mutated, KRAS can fail to deactivate, leading to uncontrolled cell growth and signaling, causing cancerous growths.

Mutations of KRAS proteins occur in approximately 25 percent of all human cancers, including more than 90 percent of pancreatic cancers and approximately 25 percent of lung cancers. Despite its prevalence as an oncogene, K-Ras’s lack of clear binding sites has made K-Ras one of the most challenging and elusive targets as a cancer therapeutic.

The KRAS Clark group plans to synthesize a variety of benzimidazole derivatives, molecules that have shown potential in inhibiting the K-Ras protein, and plan on testing the compounds' effectiveness through a wide array of bio-assays. These include the use of HCT116 cells to test for anti-proliferative activity, the use of MTT Assays to trach morphological change, and potentially even SDS-PAGE and Western Blots in order to track the ligands mechanisms.