Eribulin mesylate

Huyck, Timothy K.; Gradishar, William J.; Manuguid, Fil; Kirkpatrick, Peter

doi:10.1038/nrd3389

Cited by 85 publications

(52 citation statements)

References 11 publications

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“…The sites of recurrence were the lung in 3 patients, liver in 2, bone in 1, brain in 1, supraclavicular lymph nodes in 1, infraclavicular lymph nodes in 1 and mediastinal lymph nodes in 1. The median number of prior treatment regimens was 5 (range, [5][6][7][8][9][10][11].…”

Section: Methodsmentioning

confidence: 99%

“…The drug induces an irreversible mitotic block, which leads to cell cycle arrest in the G 2 /M phase and apoptosis (8). It is distinguished mechanistically from other antimicrotubule agents, such as paclitaxel, ixabepilone and vinblastine (9). Additionally, the drug has potent antiproliferative effects against several different types of human cancer cell lines, including breast, prostate, melanoma and colorectal cancer (10,11), and has evolved activity against paclitaxel-resistant cell lines, including those with mutations in β-tubulin (12).…”

Section: Introductionmentioning

confidence: 99%

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Examination of the clinical efficacy of eribulin and trastuzumab in HER2-positive recurrent breast cancer

Kiba

Morii

Takahashi

et al. 2015

Molecular and Clinical Oncology

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Examination of the clinical efficacy of eribulin and trastuzumab in HER2-positive recurrent breast cancer

Kiba

Morii

Takahashi

et al. 2015

Molecular and Clinical Oncology

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“…However, the very limited availability impairs this marine natural product for its therapeutic application [89]. Eribulin mesylate (E7389, or Halaven ® , 31), a synthetic analog of 30, was approved in 2010 by FDA for the treatment of locally advanced and metastatic breast cancer by inhibiting the microtubules [89,90], and was reported as a P-gp substrate [91]. The structure of 31 ( Figure 7) is complex, containing several oxygen heterocycles, two exocyclic methylene groups, a ketal group, and a pyran ring with trans ring junction, along with 15 stereogenic centers.…”

Section: Halicondrin B and Derivativesmentioning

confidence: 99%

“…Generally, the synthetic pathway of 31 consists of preparation of two fragments, i.e., C-1-C-13 and C-14-C-26, as described by Kishi's group in 1992, and one key fragment (C-27 to C-35). The final assembly strategy is accomplished by the coupling reaction depicted in Scheme 6 [90,93]. Different methods for the synthesis, to obtain milligram to gram amounts of 31 have been reported [75,93].…”

Section: Halicondrin B and Derivativesmentioning

confidence: 99%

Marine Natural Products as Models to Circumvent Multidrug Resistance

et al. 2016

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Multidrug resistance (MDR) to anticancer drugs is a serious health problem that in many cases leads to cancer treatment failure. The ATP binding cassette (ABC) transporter P-glycoprotein (P-gp), which leads to premature efflux of drugs from cancer cells, is often responsible for MDR. On the other hand, a strategy to search for modulators from natural products to overcome MDR had been in place during the last decades. However, Nature limits the amount of some natural products, which has led to the development of synthetic strategies to increase their availability. This review summarizes the research findings on marine natural products and derivatives, mainly alkaloids, polyoxygenated sterols, polyketides, terpenoids, diketopiperazines, and peptides, with P-gp inhibitory activity highlighting the established structure-activity relationships. The synthetic pathways for the total synthesis of the most promising members and analogs are also presented. It is expected that the data gathered during the last decades concerning their synthesis and MDR-inhibiting activities will help medicinal chemists develop potential drug candidates using marine natural products as models which can deliver new ABC transporter inhibitor scaffolds.

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“…1 Even in recent days, natural products have still continued to enter clinical trials or to be approved to market, including Trabectedin (ET-743), 2 Halaven (eribulin mesylate), 3,4 Bryostatin 5 and so on. It is believed that the huge chemical structure diversity and the biodiversity of natural products make the greatest contributions to the success of natural products.…”

Section: Introductionmentioning

confidence: 99%

Natural Products Remain an Important Source for Drug Development in the Post-Genomic Era

Liu

Wang

2017

MOJBB

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Abbreviations: BGCs, biosynthetic gene clusters; antiS-MASH, antibiotics and secondary metabolite analysis shell; iChip, isolation chip; PK(S), polyketide (synthase); NRP(S), nonribosomal peptide (synthase) IntroductionDrug discovery, the first critical step to identify rational lead candidates in the novel drug development, has always been a challenging, time-consuming and laborious scientific task requiring expertise and experience. Historically, natural products or their related derivatives were the main source of officially-approved drugs, with more than 50% of clinical drugs approved between 1981and 2014 were derived from natural products.1 Even in recent days, natural products have still continued to enter clinical trials or to be approved to market, including Trabectedin (ET-743), 2 Halaven (eribulin mesylate), 3,4 Bryostatin 5 and so on. It is believed that the huge chemical structure diversity and the biodiversity of natural products make the greatest contributions to the success of natural products. However, combinatorial chemistries and high-throughput screening in drug discovery over the past decades have darkened the honorable outlook of natural products to some extent, 6 which lead to the growing studies on the novel drug discovery methods in the post-genomic era. Drug discovery in the post-genomic eraWith the growing development of DNA sequencing and synthetic biology technologies (e.g. proteomics, metabolomics, bioinformatics), great interest has been renewed in natural product discovery.7 It has been already accepted that natural products are synthesized by specific metabolic pathways encoded by biosynthetic gene clusters (BGCs), based on which virtually all natural products could be identified by DNA sequencing and metagenomic analysis theoretically. In this view, the chemical space could be far more covered and much more novel chemical structures might be discovered such as those encoded by silent biosynthetic gene clusters and uncultured microorganisms.Genomics-driven natural product discovery usually includes three main steps: a. Identification of BGCs. Antibiotics from microbes or plants are directly linked to BGCs coding for proteins associated with biosynthesis, resistance, regulation and transport. So how to prioritize and characterize orphan BGCs is the first crucial procedure from the growing genome sequences. 8,9 Genome mining 10,11 is a novel technology developed for the identification and characterization of orphan BGCs, which is designed to analyze the sequenced genome of specific organisms to identify and determine whether the gene clusters involved in the production of new antibiotics. Several bioinformatics approaches have been proposed to satisfy this purpose, such as HMMER, GOLD, NORINE, SBSPKS, SEARCHPKS, NRPSpedictor 2 , plantiSMASH and so on, among which AntiSMASH (antibiotics and secondary metabolite analysis shell) 12 might be the most widely tools used. It is a comprehensive bioinformatic tool for automated genome mining including the annotation of entire gene clusters.b...

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Eribulin mesylate

Cited by 85 publications

References 11 publications

Examination of the clinical efficacy of eribulin and trastuzumab in HER2-positive recurrent breast cancer

Examination of the clinical efficacy of eribulin and trastuzumab in HER2-positive recurrent breast cancer

Marine Natural Products as Models to Circumvent Multidrug Resistance

Natural Products Remain an Important Source for Drug Development in the Post-Genomic Era

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