Miscellaneous Mechanisms Of Action Research Articles

Marine Pharmacology in 2019-2021: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis and Antiviral Activities; Affecting the Immune and Nervous Systems, and Other Miscellaneous Mechanisms of Action.

The current 2019-2021 marine pharmacology literature review provides a continuation of previous reviews covering the period 1998 to 2018. Preclinical marine pharmacology research during 2019-2021 was published by researchers in 42 countries and contributed novel mechanism-of-action pharmacology for 171 structurally characterized marine compounds. The peer-reviewed marine natural product pharmacology literature reported antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral mechanism-of-action studies for 49 compounds, 87 compounds with antidiabetic and anti-inflammatory activities that also affected the immune and nervous system, while another group of 51 compounds demonstrated novel miscellaneous mechanisms of action, which upon further investigation, may contribute to several pharmacological classes. Thus, in 2019-2021, a very active preclinical marine natural product pharmacology pipeline provided novel mechanisms of action as well as new lead chemistry for the clinical marine pharmaceutical pipeline targeting the therapy of several disease categories.

The Marine Pharmacology and Pharmaceuticals Pipeline in 2020

Marine organisms continue to provide significant chemical biodiversity that contributes to both the global preclinical and clinical pharmaceutical pipelines. Thus, in December 2020, the clinical marine pharmaceutical pipeline consisted of 13 marine-derived drugs approved by the United States Food and Drug Administration (FDA) and 1 drug approved in Australia: for cancer, cytarabine (Cytosar-U®, Depocyt®, FDA-approved 1969); for herpes simplex virus, vidarabine (Vira-A®, FDA-approved 1976); for pain, ziconotide (Prialt®, FDA-approved 2004); for hypertriglyceridemia, omega-3-acid ethyl esters (Lovaza®, FDA-approved 2004, Vascepa®, FDA-approved 2012, Epanova®, FDA-approved 2014); for cancer, eribulin mesylate (Halaven®, FDA-approved 2010), brentuximab vedotin (Adcetris®, FDA-approved 2011), trabectedin (Yondelis®, FDA-approved 2015), Plitidepsin (Aplidine®, approved in Australia 2018), polatuzumab vedotin (Polivy™, FDA-approved 2019), enfortumab vedotin-ejfv (PACDEV™, FDA-approved 2019), lurbinectedin (Zepzelca™, FDA-approved 2020) and belantamab mafadotin-blmf (BlenrepTM, FDA-approved 2020). Both https://www.clinicaltrials.gov/ website as well as the pharmaceutical companies websites describing the development of marine-derived compounds currently in Phase I, Phase II and Phase III of clinical development were searched. We determined that there were 33 marine-derived compounds in active clinical trials in December 2020: 4 marine-derived compounds were in Phase III, 17 compounds in Phase II, and at least 12 compounds in Phase I, many of them auristatin-containing antibody drug conjugates. Regular updates on the clinical marine pharmaceutical pipeline will be posted on the dedicated website: https://www.midwestern.edu/departments/marinepharmacology/clinical-pipeline.xml. Providing novel leads for the marine pharmaceutical clinical pipeline is the global preclinical marine pharmacology pipeline that continues to generate considerable preclinical data on multiple pharmacological classes: Mayer, A.M.S., A.J. Guerrero, A. D. Rodríguez, O. Taglialatela-Scafati, F. Nakamura and N. Fusetani. Marine Pharmacology in 2014–2015: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action. Marine Drugs 18(5), 2019. PMID: 31861527. We thus conclude that as of December 2020, both the marine pharmacology preclinical and clinical pharmaceutical pipelines remained very active.

The Marine Pharmacology and Pharmaceuticals Pipeline in 2018

The ocean's organisms continue to deliver a chemical biodiversity that contributes to both the global preclinical and clinical pharmaceutical pipelines. Thus, in November 2018, the clinical marine pharmaceutical pipeline consisted of seven marine‐derived drugs approved by the United States Food and Drug Administration (FDA): for cancer, cytarabine (Cytosar‐U®, Depocyt®, FDA‐approved 1969); for Herpes Simplex Virus, vidarabine (Vira‐A®, FDA‐approved 1976); for pain, ziconotide (Prialt®, FDA‐approved 2004); for hypertriglyceridemia, omega‐3‐acid ethyl esters (Lovaza®, FDA‐approved 2004); for cancer, eribulin mesylate (Halaven®, FDA‐approved 2010), brentuximab vedotin (Adcetris®, FDA‐approved 2011), and trabectedin (Yondelis®, FDA‐approved 2015). The website www.clinicaltrials.gov was searched to determine marine‐derived pharmaceuticals that were in Phase I, Phase II and Phase III of clinical development in November 2018. Confirmation of our findings in the www.clinicaltrials.gov website was conducted by visiting the websites of all pharmaceutical companies supporting the development of compounds currently in Phase I, Phase II and Phase III of clinical development. Our clinical research determined that there were 25 marine‐derived compounds in active clinical trials in November 2018: 6 marine‐derived compounds were in Phase III, 10 compounds in Phase II, and at least 9 compounds in Phase I, many of them auristatin‐containing antibody drug conjugates or ADCs. Regular updates on the clinical marine pharmaceutical pipeline will be posted on the dedicated website: http://marinepharmacology.midwestern.edu/clinical_pipeline.html. Furthermore, it is important to note that the global preclinical marine pharmacology pipeline continues to generate considerable data on multiple pharmacological classes, as highlighted in a recent review: A. M. S. Mayer, A. D. Rodríguez, O. Taglialatela‐Scafati and N. Fusetani. Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti‐Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action. Marine Drugs 15 (9): 273, 2017. We thus conclude that in November 2018, both the marine pharmacology preclinical and clinical pharmaceutical pipelines continued to remain very active.Support or Funding InformationSupport by the College of Pharmacy, Vicki Sears, Pharmacology Department, College of Graduate Studies and Elizabeth Tallman, Information Technology Services, Midwestern University are gratefully acknowledged.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Marine Pharmacology and Pharmaceuticals Pipeline in 2017

The ocean's organisms continue to deliver a chemical biodiversity that contributes to both the global preclinical and clinical pharmaceutical pipelines. Thus, in November 2017, the clinical marine pharmaceutical pipeline consisted of six marine‐derived drugs approved by the United States Food and Drug Administration (FDA): for cancer, cytarabine (Cytosar‐U®, Depocyt®, FDA‐approved 1969); for pain, ziconotide (Prialt®, FDA‐approved 2004); for hypertriglyceridemia, omega‐3‐acid ethyl esters (Lovaza®, FDA‐approved 2004); for cancer, eribulin mesylate (Halaven®, FDA‐approved 2010), brentuximab vedotin (Adcetris®, FDA‐approved 2011), and trabectedin (Yondelis®, FDA‐approved 2015). Furthermore, there were 23 marine‐derived compounds in clinical trials: 6 marine‐derived compounds in Phase III, 8 compounds in Phase II, and at least 9 compounds in Phase I, many of them auristatin‐containing antibody drug conjugates. Regular updates on the clinical marine pharmaceutical pipeline are posted at http://marinepharmacology.midwestern.edu/clinPipeline.htm. Furthermore, the global preclinical marine pharmacology pipeline continues to generate considerable data on multiple pharmacological classes, as highlighted in a recent review: A. M. S. Mayer, A. D. Rodríguez, O. Taglialatela‐Scafati and N. Fusetani. Marine Pharmacology in 2012–2013: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti‐Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action. Marine Drugs 15 (9): 273, 2017. We thus conclude that in November 2017, both the marine pharmacology preclinical and clinical pharmaceutical pipelines continued to remain very active.Support or Funding InformationSupported by Midwestern University.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Marine Pharmacology in 2009–2011: Marine Compounds with Antibacterial, Antidiabetic, Antifungal, Anti-Inflammatory, Antiprotozoal, Antituberculosis, and Antiviral Activities; Affecting the Immune and Nervous Systems, and other Miscellaneous Mechanisms of Action

The peer-reviewed marine pharmacology literature from 2009 to 2011 is presented in this review, following the format used in the 1998–2008 reviews of this series. The pharmacology of structurally-characterized compounds isolated from marine animals, algae, fungi and bacteria is discussed in a comprehensive manner. Antibacterial, antifungal, antiprotozoal, antituberculosis, and antiviral pharmacological activities were reported for 102 marine natural products. Additionally, 60 marine compounds were observed to affect the immune and nervous system as well as possess antidiabetic and anti-inflammatory effects. Finally, 68 marine metabolites were shown to interact with a variety of receptors and molecular targets, and thus will probably contribute to multiple pharmacological classes upon further mechanism of action studies. Marine pharmacology during 2009–2011 remained a global enterprise, with researchers from 35 countries, and the United States, contributing to the preclinical pharmacology of 262 marine compounds which are part of the preclinical pharmaceutical pipeline. Continued pharmacological research with marine natural products will contribute to enhance the marine pharmaceutical clinical pipeline, which in 2013 consisted of 17 marine natural products, analogs or derivatives targeting a limited number of disease categories.

Marine pharmacology in 2003–4: Marine compounds with anthelmintic antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiplatelet, antiprotozoal, antituberculosis, and antiviral activities; affecting the cardiovascular, immune and nervous systems, and other miscellaneous mechanisms of action

The current marine pharmacology review that covers the peer-reviewed literature during 2003 and 2004 is a sequel to the authors' 1998–2002 reviews, and highlights the preclinical pharmacology of 166 marine chemicals derived from a diverse group of marine animals, algae, fungi and bacteria. Anthelmintic, antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antiprotozoal, antituberculosis or antiviral activities were reported for 67 marine chemicals. Additionally 45 marine compounds were shown to have significant effects on the cardiovascular, immune and nervous system as well as possessing anti-inflammatory effects. Finally, 54 marine compounds were reported to act on a variety of molecular targets and thus may potentially contribute to several pharmacological classes. Thus, during 2003–2004, research on the pharmacology of marine natural products which involved investigators from Argentina, Australia, Brazil, Belgium, Canada, China, France, Germany, India, Indonesia, Israel, Italy, Japan, Mexico, Morocco, the Netherlands, New Zealand, Norway, Panama, the Philippines, Portugal, Russia, Slovenia, South Korea, Spain, Thailand, Turkey, United Kingdom, and the United States, contributed numerous chemical leads for the continued global search for novel therapeutic agents with broad spectrum activity.

Marine pharmacology in 2000: marine compounds with antibacterial, anticoagulant, antifungal, anti-inflammatory, antimalarial, antiplatelet, antituberculosis, and antiviral activities; affecting the cardiovascular, immune, and nervous systems and other miscellaneous mechanisms of action.

During 2000 research on the pharmacology of marine chemicals involved investigators from Australia, Brazil, Canada, Egypt, France, Germany, India, Indonesia, Israel, Italy, Japan, the Netherlands, New Zealand, Phillipines, Singapore, Slovenia, South Korea, Spain, Sweden, Switzerland, United Kingdom, and the United States. This current review, a sequel to the authors' 1998 and 1999 reviews, classifies 68 peer-reviewed articles on the basis of the reported preclinical pharmacologic properties of marine chemicals derived from a diverse group of marine animals, algae, fungi, and bacteria. Antibacterial, anticoagulant, antifungal, antimalarial, antiplatelet, antituberculosis, or antiviral activity was reported for 35 marine chemicals. An additional 20 marine compounds were shown to have significant effects on the cardiovascular and nervous system, and to possess anti-inflammatory or immunosuppressant properties. Finally, 23 marine compounds were reported to act on a variety of molecular targets and thus could potentially contribute to several pharmacologic classes. Thus, as in 1998 and 1999, during 2000 pharmacologic research with marine chemicals continued to contribute potentially novel chemical leads to the ongoing global search for therapeutic agents in the treatment of multiple disease categories.