Population pharmacokinetics of kahalalide F in advanced cancer patients

Miguel-Lillo, Bernardo; Valenzuela, Belén; Peris-Ribera, J E; Soto-Matos, Arturo; Pérez-Ruixo, Juan José

doi:10.1007/s00280-015-2800-1

Cited by 19 publications

(10 citation statements)

References 40 publications

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“…Midostaurin is among the important drugs for aggressive systemic mastocytosis (ASM) treatment as a multi-target protein kinase inhibitor, and it was FDA-approved in 2017 [124,127,128,129]. Protein kinase inhibitors from the marine origin that have entered clinical trials include three kinase inhibitors (lestaurtinib [130], enzastaurin [131], CEP-1347 [14,124,127]) in phase III, three kinase inhibitors (kahalalide F [132,133], 7-hydroxystaurosporine [134,135], staurosporine [136]) in phase II and two kinase inhibitors (CEP-2563 [14,124,127], isokahalalide F [14,124,127]) in phase I clinical studies. Somewhat related, bryostatin 1 entered phase II clinical trials for testing in the treatment of Alzheimer’s Disease as a PKC activator, after it was also experimentally used in phase I trials for various forms of cancer [137,138,139].…”

Section: Discussionmentioning

confidence: 99%

A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors

Wang

Zhang

et al. 2019

Marine Drugs

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Protein kinases are validated drug targets for a number of therapeutic areas, as kinase deregulation is known to play an essential role in many disease states. Many investigated protein kinase inhibitors are natural product small molecules or their derivatives. Many marine-derived natural products from various marine sources, such as bacteria and cyanobacteria, fungi, animals, algae, soft corals, sponges, etc. have been found to have potent kinase inhibitory activity, or desirable pharmacophores for further development. This review covers the new compounds reported from the beginning of 2014 through the middle of 2019 as having been isolated from marine organisms and having potential therapeutic applications due to kinase inhibitory and associated bioactivities. Moreover, some existing clinical drugs based on marine-derived natural product scaffolds are also discussed.

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Section: Discussionmentioning

confidence: 99%

A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors

Wang

Zhang

et al. 2019

Marine Drugs

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“…Through the inhibition of the PI3K-AKT pathway, the cytotoxic activity of Kahalalide F (KF) resulted in cell death in cancer cells [124]. Also, KF potently reduced in vivo tumor growth and navigated through phase I and II clinical trials for advanced solid cancers [125,126], albeit with limited activity. Despite being discontinued from clinical trials, it paved the way for other compounds such as the deptispeptide Elisidepsin which was derived from KF synthetically.…”

Section: Mollusksmentioning

confidence: 99%

From Seabed to Bedside: A Review on Promising Marine Anticancer Compounds

et al. 2020

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The marine environment represents an outstanding source of antitumoral compounds and, at the same time, remains highly unexplored. Organisms living in the sea synthesize a wide variety of chemicals used as defense mechanisms. Interestingly, a large number of these compounds exert excellent antitumoral properties and have been developed as promising anticancer drugs that have later been approved or are currently under validation in clinical trials. However, due to the high need for these compounds, new methodologies ensuring its sustainable supply are required. Also, optimization of marine bioactives is an important step for their success in the clinical setting. Such optimization involves chemical modifications to improve their half-life in circulation, potency and tumor selectivity. In this review, we outline the most promising marine bioactives that have been investigated in cancer models and/or tested in patients as anticancer agents. Moreover, we describe the current state of development of anticancer marine compounds and discuss their therapeutic limitations as well as different strategies used to overcome these limitations. The search for new marine antitumoral agents together with novel identification and chemical engineering approaches open the door for novel, more specific and efficient therapeutic agents for cancer treatment.

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“…The marine-derived cyclic depsipeptide kahalalide F was the first compound found in algae that achieved the phase II of clinical trials (Murphy et al, 2014 ). Kahalalide F is a potent cytotoxic compound produced by the green alga Bryopsis pennata and found in the mollusk Elysia rufescens (Miguel-Lillo et al, 2015 ; Sable et al, 2017 ). It advanced through five clinical trials and completed the safety evaluation in phase I in patients with distinct advanced solid tumors.…”

Section: Antitumor Potential Of Marine Algae-derived Compoundsmentioning

confidence: 99%

From Marine Origin to Therapeutics: The Antitumor Potential of Marine Algae-Derived Compounds

et al. 2018

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Marine environment has demonstrated to be an interesting source of compounds with uncommon and unique chemical features on which the molecular modeling and chemical synthesis of new drugs can be based with greater efficacy and specificity for the therapeutics. Cancer is a growing public health threat, and despite the advances in biomedical research and technology, there is an urgent need for the development of new anticancer drugs. In this field, it is estimated that more than 60% of commercially available anticancer drugs are natural biomimetic inspired. Among the marine organisms, algae have revealed to be one of the major sources of new compounds of marine origin, including those exhibiting antitumor and cytotoxic potential. These compounds demonstrated ability to mediate specific inhibitory activities on a number of key cellular processes, including apoptosis pathways, angiogenesis, migration and invasion, in both in vitro and in vivo models, revealing their potential to be used as anticancer drugs. This review will focus on the bioactive molecules from algae with antitumor potential, from their origin to their potential uses, with special emphasis to the alga Sphaerococcus coronopifolius as a producer of cytotoxic compounds.

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Population pharmacokinetics of kahalalide F in advanced cancer patients

Cited by 19 publications

References 40 publications

A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors

A Systematic Review of Recently Reported Marine Derived Natural Product Kinase Inhibitors

From Seabed to Bedside: A Review on Promising Marine Anticancer Compounds

From Marine Origin to Therapeutics: The Antitumor Potential of Marine Algae-Derived Compounds

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