title: Cyclic depsipeptides as potential cancer therapeutics.
abstract: Cyclic depsipeptides are polypeptides in which one or more amino acid is replaced by a hydroxy acid, resulting in the formation of at least one ester bond in the core ring structure. Many natural cyclic depsipeptides possessing intriguing structural and biological properties, including antitumor, antifungal, antiviral, antibacterial, anthelmintic, and anti-inflammatory activities, have been identified from fungi, plants, and marine organisms. In particular, the potent effects of cyclic depsipeptides on tumor cells have led to a number of clinical trials evaluating their potential as chemotherapeutic agents. Although many of the trials have not achieved the desired results, romidepsin (FK228), a bicyclic depsipeptide that inhibits histone deacetylase, has been shown to have clinical efficacy in patients with refractory cutaneous T-cell lymphoma and has received Food and Drug Administration approval for use in treatment. In this review, we discuss antitumor cyclic depsipeptides that have undergone clinical trials and focus on their structural features, mechanisms, potential applications in chemotherapy, and pharmacokinetic and toxicity data. The results of this study indicate that cyclic depsipeptides could be a rich source of new cancer therapeutics.
authors.affiliation: aDepartment of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry bChallenge to Intractable Oral Diseases, Center for Translational Dental Research, Osaka University Dental Hospital, Suita, Osaka, Japan cMacromolecular Crystallography Laboratory, National Cancer Institute, National Institutes of Health, Frederick, Maryland, USA dCenter for Translational Medicine, Shanghai Changzheng Hospital, Second Military Medical University, Shanghai, People's Republic of China.
authors.forename: Jirouta
authors.initials: J
authors.lastname: Kitagaki
authors.forename: Genbin
authors.initials: G
authors.lastname: Shi
authors.forename: Shizuka
authors.initials: S
authors.lastname: Miyauchi
authors.forename: Shinya
authors.initials: S
authors.lastname: Murakami
authors.forename: Yili
authors.initials: Y
authors.lastname: Yang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D002986:Clinical Trials as Topic; D047630:Depsipeptides / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology; D006801:Humans; D007769:Lactams / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D007783:Lactones / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology; D016410:Lymphoma, T-Cell, Cutaneous / Q000188:drug therapy; D010456:Peptides, Cyclic
chemical_list: D000970:Antineoplastic Agents; D047630:Depsipeptides; D056572:Histone Deacetylase Inhibitors; D007769:Lactams; D007783:Lactones; D010456:Peptides, Cyclic; C522358:elisidepsin; C030051:didemnins; C097897:kahalalide F; C087123:romidepsin; C114033:cryptophycin 52; C510034:cryptophycin 1; C098980:plitidepsin