Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data

Bai, Ruoli; Paull, Kenneth D.; Herald, Cherry L.; Malspeis, Louis; Pettit, George R.; Hamel, Ernest

doi:10.1016/s0021-9258(18)98491-7

Cited by 336 publications

(100 citation statements)

References 22 publications

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“…Other microtubule inhibitors include taxanes, which are microtubule stabilizing agents, but these agents have had limited success in pediatric malignancies [95,96]. Eribulin is a novel microtubule inhibitor which is a synthetic analogue of the natural product halichondrin B, derived from the marine sponge Halichondria okadai [97,98]. The mechanism of eribulin is unique in that it leads to apoptosis by inhibiting the polymerization of tubulin subunits, but it does not affect microtubule shortening [99].…”

Section: Novel Cytotoxic Agents: Eribulinmentioning

confidence: 99%

Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children’s Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force

Pacenta

Allen‐Rhoades

Langenau

et al. 2021

JCM

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Rhabdomyosarcoma is the most common soft tissue sarcoma diagnosed in children and adolescents. Patients that are diagnosed with advanced or relapsed disease have exceptionally poor outcomes. The Children’s Oncology Group (COG) convened a rhabdomyosarcoma new agent task force in 2020 to systematically evaluate novel agents for inclusion in phase 2 or phase 3 clinical trials for patients diagnosed with rhabdomyosarcoma, following a similar effort for Ewing sarcoma. The task force was comprised of clinicians and basic scientists who collectively identified new agents for evaluation and prioritization in clinical trial testing. Here, we report the work of the task force including the framework upon which the decisions were rendered and review the top classes of agents that were discussed. Representative agents include poly-ADP-ribose polymerase (PARP) inhibitors in combination with cytotoxic agents, mitogen-activated protein kinase (MEK) inhibitors in combination with type 1 insulin-like growth factor receptor (IGFR1) inhibitors, histone deacetylase (HDAC) inhibitors, and novel cytotoxic agents.

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Section: Novel Cytotoxic Agents: Eribulinmentioning

confidence: 99%

Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children’s Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force

Pacenta

Allen‐Rhoades

Langenau

et al. 2021

JCM

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“…Recent studies have demonstrated that halichondrin B behaves as a tubulin‐destabilizing agent with subtle differences in mechanism of action from other antimitotics such as the vinca alkaloids 26c. 35 For example, halichondrin B noncompetitively inhibits vinca alkaloid binding to tubulin through an allosteric interaction 35.…”

Section: Halichondrinsmentioning

confidence: 99%

The Medicinal Potential of Promising Marine Macrolides with Anticancer Activity

2011

ChemMedChem

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Marine natural products have become a major source of new chemical entities in the discovery of potential anticancer agents that potently suppress various molecular targets. In particular, the marine macrolides, which include an array of novel biomolecules endowed with outstanding cytotoxic and/or antiproliferative activities, are a prominent class of marine natural products that offer continued promise for breakthroughs in anticancer research. Herein we highlight some recent studies of promising marine macrolides, paying particular attention to their discovery, anticancer activities, mechanisms of action, chemical synthesis, and representative analogues.

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“…The mechanism of action also involves blockage of the binding site for the Vinca alkaloids, D-10 and its analogues. It also inhibits GTP hydrolysis and the nucleotide exchange mechanism, blocking the cancer cell cycle in the G2 phase [114]. H-D is active against a wide variety of cancer cell lines, melanomas, sarcomas, and lung and colon cancers in vivo [115].…”

Section: Halichondrin B (H-b)mentioning

confidence: 99%

Pharmacological Developments Obtained from Marine Natural Products and Current Pipeline Perspective

Galeano

Rojas

Martínez

2011

Natural Product Communications

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Marine organisms represent a new extensive source for bioactive molecules. They have the potential to provide new therapeutic alternatives to treat human diseases. In this paper, we describe and discuss a variety of isolated and semisynthetic molecules obtained from marine sources. These compounds are in phase II, phase III and at the commercialization stage of new drug development. A description of the mechanism of action, dosage used and side effects are also reported. The positive results obtained from these studies have triggered the development of new studies to evaluate the prospects for utilization of marine organisms.

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Halichondrin B and homohalichondrin B, marine natural products binding in the vinca domain of tubulin. Discovery of tubulin-based mechanism of action by analysis of differential cytotoxicity data

Cited by 336 publications

References 22 publications

Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children’s Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force

Prioritization of Novel Agents for Patients with Rhabdomyosarcoma: A Report from the Children’s Oncology Group (COG) New Agents for Rhabdomyosarcoma Task Force

The Medicinal Potential of Promising Marine Macrolides with Anticancer Activity

Pharmacological Developments Obtained from Marine Natural Products and Current Pipeline Perspective

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