The bioactive
natural product seriniquinone was discovered as a potential
melanoma drug, which was produced by the as-yet-undescribed marine bacterium of the rare genus Serinicoccus. As part of a long-term research program aimed at the discovery of new agents for the treatment of
cancer,
seriniquinone revealed remarkable in vitro activity against a diversity of
cancer cell lines in the US National Cancer Institute 60-cell line screening. Target deconvolution studies defined the seriniquinones as a new class of
melanoma-selective agents that act in part by targeting
dermcidin (
DCD). The targeted
DCD peptide has been recently examined and defined as a "pro-survival
peptide" in
cancer cells. While
DCD was first isolated from human skin and thought to be only an
antimicrobial peptide, currently
DCD has been also identified as a
peptide associated with the survival of
cancer cells, through what is believed to be a
disulfide-based conjugation with
proteins that would normally induce apoptosis. However, the significantly enhanced potency of
seriniquinone was of particular interest against the
melanoma cell lines assessed in the NCI 60-cell line panel. This observed selectivity provided a driving force that resulted in a multidimensional program for the discovery of a usable
drug with a new anticancer target and, therefore, a novel mode of action. Here, we provided an overview of the discovery and development efforts to date.