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- Title
Preclinical Development of Seriniquinones as Selective Dermcidin Modulators for the Treatment of Melanoma.
- Authors
Hirata, Amanda S.; La Clair, James J.; Jimenez, Paula C.; Costa-Lotufo, Leticia Veras; Fenical, William
- Abstract
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.
- Subjects
NATIONAL Cancer Institute (U.S.); ANTIMICROBIAL peptides; CANCER cells; PEPTIDES; MELANOMA; MARINE natural products; MARINE bacteria
- Publication
Marine Drugs, 2022, Vol 20, Issue 5, p301
- ISSN
1660-3397
- Publication type
Article
- DOI
10.3390/md20050301