Demethylmycemycin A, a dibenzoxazepinone from the marine-derived Dactylosporangium sp. OK1079, with prostate cancer suppressive effects via targeting BRK-FAK-STAT3 axis.

Marwa Elsbaey, Md Towhidul Islam Tarun, Radwan Alnajjar, Takahiro Jomori, Junichi Tanaka, Naoya Oku, Khalid El Sayed, Yasuhiro Igarashi

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Article in The Journal of antibiotics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

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8 authors.

Marwa Elsbaey *Pharmacognosy Department, Faculty of Pharmacy, Mansoura University, Mansoura, 35516, Egypt. marwaelsebay1611@mans.edu.eg.

Md Towhidul Islam Tarun *School of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, 71201, USA.

Radwan AlnajjarDepartment of Chemistry, Faculty of Science, University of Benghazi, Benghazi, 16063, Libya.

Takahiro JomoriDepartment of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, Nishihara, Okinawa, 903-0213, Japan.

Junichi TanakaDepartment of Chemistry, Biology and Marine Science, Faculty of Science, University of the Ryukyus, Nishihara, Okinawa, 903-0213, Japan.

Naoya OkuBiotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan.ORCID http://orcid.org/0000-0002-2171-2168

Khalid El SayedSchool of Basic Pharmaceutical and Toxicological Sciences, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, 71201, USA.ORCID http://orcid.org/0000-0002-1456-4064

Yasuhiro IgarashiBiotechnology Research Center and Department of Biotechnology, Toyama Prefectural University, 5180 Kurokawa, Imizu, Toyama, 939-0398, Japan.ORCID http://orcid.org/0000-0001-5114-1389

Funding

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6 · The paper itself

Abstract

Breast tumor kinase (Brk) is an intracellular kinase that initiates a downstream oncogenic signaling through phosphorylation of focal adhesion kinase (FAK) and signal transducer and activator of transcription 3 (STAT3). Demethylmycemycin A (DA) was isolated from a sponge-derived Dactylosporangium sp. OK1079. Though known as a microbial dibenzoxazepinone, its biological activity has never been investigated. Previous studies on the marine triterpene sipholenol A identified its perhydrobenzoxepine system as the key pharmacophore that mediated its Brk binding. The bioisosteric similarity of DA to the sipholenol A perhydrobenzoxepine motivated a molecular docking simulation of DA for potential Brk binding. The antiproliferative effect of DA was investigated against diverse prostate cancer (PC) cell lines including LNCaP (castration/hormone-sensitive primary adenocarcinoma), PC3, and 22Rv1 (castration-resistant), in addition to the androgen-independent DU145 cells. LNCaP cells were the most sensitive to the effects of DA, followed by PC3, showing IC

Indexed as

Antineoplastic AgentsProstatic NeoplasmsSTAT3 Transcription FactorAnimalsCell Line, TumorCell ProliferationFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesHumansMaleMolecular Docking SimulationPoriferaSignal TransductionAntineoplastic AgentsFocal Adhesion Kinase 1Focal Adhesion Protein-Tyrosine KinasesPTK2 protein, humanSTAT3 protein, humanSTAT3 Transcription Factor

Identifiers

PMID41198947

DOI10.1038/s41429-025-00871-2

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.