Small Molecule NOX Inhibitors of Human Melanoma Cell Proliferation

Derivatives of Triphenylmethane Dyes and Their Use in Treating Cancer

ApplicationTriphenylmethane small molecules inhibiting NADPH oxidase (NOX) for the anti-proliferation of melanoma tumor cells.Key BenefitsModifies molecular interactions with cellular proteins, reducing cell tumor growth.Compounds are capable of inhibiting cell proliferation to a greater extent than current competing NOX inhibitors for melanoma cells.Market SummarySkin cancer accounts for approximately one third of all cancers in the U.S. with over 132,000 cases of melanoma diagnosed annually. In over 60% of these cases, Melanomas express a mutation, leading to uncontrolled cell growth. In cases with the mutation, late stage melanoma patients are administered vemurafenib, but nearly 40% of these melanomas develop resistance to the drug. The other option includes immunotherapies with significant side effects, high toxicity, and increased resistance. Recent research suggests that reactive oxygen species (ROS) play a role in melanomagenesis and inflammation. Reactive oxygen-driven tumors utilize the NADPH oxidase (NOX) signaling pathway in tumor growth, thus a potential treatment for these tumors include blockage of reactive oxygen using NOX inhibitors.Technical SummaryEmory inventor, Jack Arbiser, has developed two small molecules in the triphenylmethane family that have been shown to be potent inhibitors of NOX. The anti-proliferative potential of the compounds has been studied in three different human melanoma cell lines, including a cell line that has acquired vemurafenib resistance. The two compounds have distinct functional groups that modify molecular interactions with cellular proteins involved in proliferation. Both compounds were found to inhibit cell proliferation in the human melanoma cell lines and may have potential in other cancers.Developmental StageSmall molecules have been synthesized and characterized for anti-proliferative potential.Structural motifs and in vitro responses are under development.

Oct 23, 2015

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