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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
Another anti-cancer metabolite, Bryostatin 1, a 26-numbered macrocyclic lactone was isolated [225]. Bryostatin 1 is a partial agonist of protein kinase C and showed potent activity on human tumor xenografts in vivo. It has been developed predominantly by the NCI for the treatment of melanoma, non-Hodgkins lymphoma, and renal cancer and is currently in Phase II clinical trials in the United States [117].
Matrix metalloproteinases
Published in A. R. Genazzani, Hormone Replacement Therapy and Cancer, 2020
S. McDonnell, A. O’Connor, D. Murray, C. C. Lynch
Currendy, a number of MMP inhibitors have been developed and some are in clinical trials as anti-metastatic or anti-cancer therapies. Although many of the initial trials were quite promising, some complications have become apparent in the human trials, with the most severe side-effect being tendonitis in the joints of the shoulders, hands and knees39,40. These results indicate the necessity for further investigation into the normal biological functions of MMPs. Marimastat®, a potent broadspectrum inhibitor of MMPs, proved to be effective in phase I and II trials against colon, ovarian, prostate, lung and pancreatic cancers. Recently, phase III clinical trials involving Marimastat were halted as it was found to be performing worse than the placebo. The bryostatins are a group of naturally occurring macrocyclic lactones which inhibit MMP activity through down-regulation of the protein kinase C pathway. Recently, a number of investigators have begun testing bryostatin compounds for their effectiveness as tumoristatic agents. AG3340/prinostatin has been shown to inhibit the proliferation and invasion of glioma cells in vitro41. In early 2001, phase III clinical trials which were examining the effects of prinostatin on prostate and lung cancers were halted. Phase II trials involving patients with earlier stages of the disease, however, are set to continue.
Biological Response Modifiers and Chemotherapeutic Agents that Alter Interleukin 2 Activities
Published in Ronald H. Goldfarb, Theresa L. Whiteside, Tumor Immunology and Cancer Therapy, 2020
William L. West, Allen R. Rhoads, Clement O. Akogyeram
Bryostatins are macrocyclic lactones extracted and chemically purified from marine bryozoans, sea mosses (38). Synthetic phorbol myristate and natural bryostatins activated protein kinase C (PKC), an intracellular enzyme important in lymphocyte activation (39,40). Unlike tumor-promoting phorbol esters, bryostatins are antineoplastic. Bryostatins induce transcriptional activation of the IL2R gene and down-regulate certain specific T-cell surface markers. Bryostatins are also able to block some biochemical responses caused by phorbol esters.
SARS, MERS and SARS-CoV-2 (COVID-19) treatment: a patent review
Published in Expert Opinion on Therapeutic Patents, 2020
José Adão Carvalho Nascimento Junior, Anamaria Mendonça Santos, Lucindo José Quintans-Júnior, Cristiani Isabel Banderó Walker, Lysandro Pinto Borges, Mairim Russo Serafini
Finally, one patent reported the use of bryostatin-1, a substance from the marine benthic animal Bugula neritinac, to treat SARS-CoV-1. This is the first macrolide compound with anti-cancer activity, having strong therapeutic properties in the treatment of leukemias, renal, cervical cancers, melanoma, and lymphomas. It can also be used to treat atypical pneumonia present in the clinical picture of CoVs [72].
Clinical pharmacology in HIV cure research – what impact have we seen?
Published in Expert Review of Clinical Pharmacology, 2019
Andrea Giacomelli, Sonia de Rose, Stefano Rusconi
Other key molecular mechanisms involved in HIV-1 latency are sequestration of transcription initiation/elongation factors and blockade of the assembly of the active elongation factor, P-TEFb. The NF-κB pathway appears to be one of the most relevant pathways concerning HIV-1 reactivation. Protein kinase C agonists (PKCA) activate PKC isoforms which then phosphorylate IκB and consequently activate NF-κB. Several PKC agonists have been considered for purging the reservoirs of latent HIV-1 [61]. First of all, prostratin is a unique phorbol ester that it induces potent T cell activation signals and is not tumorigenic. Besides the ability of prostratin to induce T-cell activation through PKC, without tumor-promoting ability, another unique property is that, despite being able to reactivate latent HIV-1, it exerts an inhibitory effect on active HIV-1 replication through downregulation of CD4 [62]. Furthermore, bryostatin-1 has appeared to be an effective reversing agent. Bryostatins represent an important group of pharmaceutically promising substances. These compounds are produced by commensal microorganisms naturally occurring in marine invertebrates, mainly in bryozoans. The most frequently investigated substance is bryostatin-1, which is a highly oxygenated macrolide with a polyacetate backbone [63]. Its mechanism of action involves a bound to the diacylglycerol-binding region within the C-1 regulatory domain of PKC. Bryostatin-1 has shown to reactivate latent HIV-1 in vitro in monocytoid and lymphoid cell line models of latency and was approximately 1,000-fold more potent than prostratin [62]. However, since economic and environmental factors have severely limited its availability, De Cristopher et al. reported the activity of seven bryostatin-1 analogs, dubbed ‘bryologs’, specifically designed to obtain molecules easier to operate with. These compounds incorporate a tetrahydropyranyl B-ring formed through a versatile prins macrocyclization. They demonstrated that these simplified bryostatin analogs, which share the functional activity of the clinical candidate prostratin, are up to four orders of magnitude more potent [64].