China
Africa
Explore chapters and articles related to this topic
Antitubulin Agents
Published in David E. Thurston, Ilona Pysz, Chemistry and Pharmacology of Anticancer Drugs, 2021
Halichondrin B, a large polyether macrolide with a molecular weight of 1,110 (Figure 4.9), is a natural product originally isolated from the marine sponge Halichondria okadai (Lissodendoryx sp.) by Hirata and Uemura in the 1980s working at the National Cancer Center Research Institute in Tokyo (Japan). It was shown to be a potent mitotic inhibitor with a unique mechanism of action and to have significant cytotoxicity toward murine tumor cells in culture and antitumor activity in in vivo studies. Halichondrin B was prioritized for development as a novel anticancer agent by the NCI (NSC-707389), and in 1991, it became the first cytotoxic agent to have its mechanism of action (in this case, tubulin-targeted mitotic inhibition) identified through the NCI’s new (at the time) “60-cell line screen”. Structure of halichondrin B, showing the pharmacophore that provides the basis of the structure of eribulin (HavalenTM).
Marine Natural Products for Human Health Care
Published in Hafiz Ansar Rasul Suleria, Megh R. Goyal, Health Benefits of Secondary Phytocompounds from Plant and Marine Sources, 2021
In recent years, more, and more researchers are involved in the research on marine organisms with potential as a source of novel molecules and new anticancer agents [306]. According to recent reports, more than 10 novel marine anti-tumor agents have entered clinical trials [330], such as bryostatin-1, aplidine, ecteinascidin-743 (ET-743), Kahalalide F as well as derivatives of dolastatin (such as TZT-1027 and LU 103793). A synthetic analog of C-nucleoside (cytarabine or Ara-C) from the Caribbean sponge (Cryptothethya crypta) was the first marine derived anticancer agent developed for clinical use. It was approved in 1969 and currently in use for the treatment of acute myelocytic leukemia and non-Hodgkin’s lymphoma [250, 258]. A third discovery from marine source was halichondrin A (a polyether metabolite from the sponge, Halichondria okadai) [119].
Marine Natural Products and Chemistry
Published in Se-Kwon Kim, Marine Biochemistry, 2023
Jeyapragash Danaraj, Saravanakumar Ayyappan
Bryostatin is a polyketide isolated from the bryozoan Buguna neritina, which is effective in both anticancer and immune-modulating activity (Suffness et al., 1989). Its mechanism of action is via the activation of protein kinase C-mediated cell-signal transduction pathways. The drug is under the clinical trial of phase II for chronic lymphocytic leukemia. Non-Hodgkin’s lymphoma and multiple myeloma via a cooperative research and development agreement between the National Cancer Institute (NCI) and Bristol Myers Squibb. Ecteinascidin-743, an alkaloid isolated from the ascidian Ecteinascidia turbinate, is under the phase I clinical trial for ovarian cancer. Discodermolide, a polyketide isolated from marine sponges of the class Discodermia, acts as an immunosuppressive and anticancer agent that inhibits cell proliferation by intrusion of the cells’ microtubule network (Hart, 1997). It is also effective against breast cancer and has been licensed by the Harbor Branch Oceanographic Institution and Novartis Pharmaceutical Corporation. Another promising compound from the marine sponge is halichondrin B, isolated from marine sponge from New Zealand, Lissodendoryx sp. Apart from the previously mentioned drugs, many secondary metabolites, such as alkaloids, terpenoids, polyketides, peptides, steroids, sugars, and shikimic acid derivatives, were isolated from marine sponges and still research goes on in order to identify their biological activities, including anti-microbial, anti-tumor, anti-diabetic, anti-inflammatory, anti-malarial, anti-fouling, and anti-protozoal, with higher industrial and therapeutic potential (Mayer et al., 2017; Agrawal et al., 2018).
The safety of eribulin for the treatment of metastatic breast cancer
Published in Expert Opinion on Drug Safety, 2019
Jose Manuel Perez-Garcia, Javier Cortes
Eribulin mesylate (also known as eribulin, ER-086526, and E7389) is a synthetic macrocyclic ketone analogue of the marine sponge product halichondrin B [1–3]. Halichondrin B was shown to have exceptional potency during in vivo experiments with murine melanoma and leukemia, demonstrating its high cytotoxicity [1,4]. The cytotoxic potency of halichondrin B originates from its macrocyclic lactone C1–C38 moiety; thus, eribulin retains the activity of its parent molecule despite having a simplified structure [1]. Eribulin demonstrated subnanomolar potency with respect to growth inhibition of human cancer cells of multiple tumor types [1]. In vivo anticancer efficacy of eribulin at doses below 1 mg/kg was also demonstrated in several human tumor xenograft models including breast, colon, melanoma, glioblastoma, and ovarian cancer [1,5].
Chemotherapy and targeted treatments of breast sarcoma by histologic subtype
Published in Expert Review of Anticancer Therapy, 2021
Stefania Kokkali, Athina Stravodimou, Jose Duran-Moreno, Nektarios Koufopoulos, Ioannis a Voutsadakis, Antonia Digklia
Eribulin is another newer drug, initially used in BC. It is a non-taxane microtubule inhibitor and an analogue of halichondrin B originated from the marine sponge Halichondria okadai. In a randomized phase III study of patients with L-sarcomas who had received two or more previous treatments, eribulin administration resulted in an improved OS versus dacarbazine (13.5 v. 11.5 months, HR: 0.77, 95% CI: 0.62–0.95) [52]. Subgroup analysis in liposarcoma patients confirmed both PFS and OS improvement with HR of 0.52 and 0.51, respectively [53]. Currently, there are no specific data on BS in any of these trials regarding trabectedin or eribulin, with only some case reports being published [54,55].
Metabolomic tools used in marine natural product drug discovery
Published in Expert Opinion on Drug Discovery, 2020
Kevin Andrew Stuart, Keira Welsh, Molly Clare Walker, RuAngelie Edrada-Ebel
Yondelis® (trabectedin®), a novel alkaloid with a unique mechanism of action as it acts to bind the minor groove of the DNA supercoil and inhibit DNA repair machinery [2,6]. It was isolated from the tunicate Ecteinascidia turbinata [3].Halaven® (erbulin mesylate), used in metastatic breast cancer, is a synthetic analog of the cytotoxic halichondrin B, isolated from the sponge Halichondria okadai [3].