{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:49:32Z","timestamp":1791812972013,"version":"4.3.4"},"reference-count":52,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochemical Pharmacology"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.bcp.2026.118518","type":"journal-article","created":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T22:06:35Z","timestamp":1791151595000},"page":"118518","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"P3","title":["3-Methoxychrysazin suppresses RANKL-induced osteoclastogenesis by modulating Notch2 signaling"],"prefix":"10.1016","volume":"254","author":[{"given":"Da Eun","family":"Lee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeo Rang","family":"Cho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki Hyun","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil-Saeng","family":"Jeong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.bcp.2026.118518_b0005","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1159\/000380991","article-title":"Physiology of bone","volume":"28","author":"Grabowski","year":"2015","journal-title":"Endocr. Dev."},{"key":"10.1016\/j.bcp.2026.118518_b0010","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1196\/annals.1365.035","article-title":"Bone remodeling","volume":"1092","author":"Hadjidakis","year":"2006","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.bcp.2026.118518_b0015","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1007\/978-981-13-1117-8_12","article-title":"Aging of the bone","volume":"1086","author":"Wei","year":"2018","journal-title":"Adv. Exp. Med. Biol."},{"key":"10.1016\/j.bcp.2026.118518_b0020","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1080\/03008207.2017.1290085","article-title":"Osteoblast-osteoclast interactions","volume":"59","author":"Chen","year":"2018","journal-title":"Connect. Tissue Res."},{"key":"10.1016\/j.bcp.2026.118518_b0025","doi-asserted-by":"crossref","first-page":"2073","DOI":"10.3390\/cells9092073","article-title":"Osteoblast-osteoclast communication and bone homeostasis","volume":"9","author":"Kim","year":"2020","journal-title":"Cells"},{"key":"10.1016\/j.bcp.2026.118518_b0030","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1111\/nyas.13572","article-title":"Bone quality changes associated with aging and disease: a review","volume":"1410","author":"Boskey","year":"2017","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"10.1016\/j.bcp.2026.118518_b0035","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.abb.2008.03.018","article-title":"Functions of RANKL\/RANK\/OPG in bone modeling and remodeling","volume":"473","author":"Boyce","year":"2008","journal-title":"Arch. Biochem. Biophys."},{"key":"10.1016\/j.bcp.2026.118518_b0040","doi-asserted-by":"crossref","first-page":"706","DOI":"10.14348\/molcells.2017.0225","article-title":"Current understanding of RANK signaling in osteoclast differentiation and maturation","volume":"40","author":"Park","year":"2017","journal-title":"Mol. Cells"},{"key":"10.1016\/j.bcp.2026.118518_b0045","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/j.molmed.2005.11.007","article-title":"RANKL-RANK signaling in osteoclastogenesis and bone disease","volume":"12","author":"Wada","year":"2006","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.bcp.2026.118518_b0050","first-page":"3","article-title":"Bone: oxidative stress and osteoporosis","volume":"10","author":"Wilson","year":"2014","journal-title":"Nat. Rev. Endocrinol."},{"key":"10.1016\/j.bcp.2026.118518_b0055","doi-asserted-by":"crossref","first-page":"468","DOI":"10.1016\/j.molmed.2009.08.004","article-title":"Oxidative stress in bone remodelling and disease","volume":"15","author":"Wauquier","year":"2009","journal-title":"Trends Mol. Med."},{"key":"10.1016\/j.bcp.2026.118518_b0060","doi-asserted-by":"crossref","first-page":"R129","DOI":"10.1016\/j.cub.2004.01.023","article-title":"Regulation of notch signaling activity","volume":"14","author":"Schweisguth","year":"2004","journal-title":"Curr. Biol."},{"key":"10.1016\/j.bcp.2026.118518_b0065","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/bs.ircmb.2015.12.002","article-title":"Regulation of notch signaling through intracellular transport","volume":"323","author":"Conner","year":"2016","journal-title":"Int. Rev. Cell Mol. Biol."},{"key":"10.1016\/j.bcp.2026.118518_b0070","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1126\/science.284.5415.770","article-title":"Notch signaling: cell fate control and signal integration in development","volume":"284","author":"Artavanis-Tsakonas","year":"1999","journal-title":"Science"},{"key":"10.1016\/j.bcp.2026.118518_b0075","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1016\/0092-8674(95)90294-5","article-title":"Jagged: a mammalian ligand that activates Notch1","volume":"80","author":"Lindsell","year":"1995","journal-title":"Cell"},{"key":"10.1016\/j.bcp.2026.118518_b0080","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.cell.2009.03.045","article-title":"The canonical Notch signaling pathway: unfolding the activation mechanism","volume":"137","author":"Kopan","year":"2009","journal-title":"Cell"},{"key":"10.1016\/j.bcp.2026.118518_b0085","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1093\/intimm\/dxf030","article-title":"Inducible gene knockout of transcription factor recombination signal binding protein-J reveals its essential role in T versus B lineage decision","volume":"14","author":"Han","year":"2002","journal-title":"Int. Immunol."},{"key":"10.1016\/j.bcp.2026.118518_b0090","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1038\/nrm2009","article-title":"Notch signalling: a simple pathway becomes complex","volume":"7","author":"Bray","year":"2006","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"10.1016\/j.bcp.2026.118518_b0095","doi-asserted-by":"crossref","unstructured":"M. Ehebauer, P. Hayward, A. Martinez-Arias, Notch signaling pathway, Sci STKE 2006 (2006) cm7, https:\/\/doi.org\/10.1126\/stke.3642006cm7.","DOI":"10.1126\/stke.3642006cm7"},{"key":"10.1016\/j.bcp.2026.118518_b0100","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41392-022-00934-y","article-title":"Notch signaling pathway: architecture, disease, and therapeutics","volume":"7","author":"Zhou","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"10.1016\/j.bcp.2026.118518_b0105","doi-asserted-by":"crossref","first-page":"2611","DOI":"10.1007\/s00198-018-4694-3","article-title":"Notch in skeletal physiology and disease","volume":"29","author":"Canalis","year":"2018","journal-title":"Osteoporos Int."},{"key":"10.1016\/j.bcp.2026.118518_b0110","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1016\/j.ajpath.2019.05.005","article-title":"Notch signaling in osteogenesis, osteoclastogenesis, and angiogenesis","volume":"189","author":"Luo","year":"2019","journal-title":"Am. J. Pathol."},{"key":"10.1016\/j.bcp.2026.118518_b0115","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2022.115377","article-title":"The role of Notch signaling pathway in metabolic bone diseases","volume":"207","author":"Gao","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.bcp.2026.118518_b0120","doi-asserted-by":"crossref","DOI":"10.1016\/j.bone.2020.115474","article-title":"Notch and the regulation of osteoclast differentiation and function","volume":"138","author":"Yu","year":"2020","journal-title":"Bone"},{"key":"10.1016\/j.bcp.2026.118518_b0125","doi-asserted-by":"crossref","first-page":"357","DOI":"10.1016\/j.cellsig.2016.01.016","article-title":"Notch2 signaling promotes osteoclast resorption via activation of PYK2","volume":"28","author":"Jin","year":"2016","journal-title":"Cell. Signal."},{"key":"10.1016\/j.bcp.2026.118518_b0130","doi-asserted-by":"crossref","first-page":"18245","DOI":"10.1074\/jbc.M610701200","article-title":"NF-kappaB p50 and p52 regulate receptor activator of NF-kappaB ligand (RANKL) and tumor necrosis factor-induced osteoclast precursor differentiation by activating c-Fos and NFATc1","volume":"282","author":"Yamashita","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bcp.2026.118518_b0135","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1038\/aps.2015.85","article-title":"Aconine inhibits RANKL-induced osteoclast differentiation in RAW264.7 cells by suppressing NF-\u03baB and NFATc1 activation and DC-STAMP expression","volume":"37","author":"Zeng","year":"2016","journal-title":"Acta Pharmacol. Sin."},{"key":"10.1016\/j.bcp.2026.118518_b0140","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1186\/ar2165","article-title":"Biology of RANK, RANKL, and osteoprotegerin","volume":"9","author":"Boyce","year":"2007","journal-title":"Arthritis Res. Ther."},{"key":"10.1016\/j.bcp.2026.118518_b0145","doi-asserted-by":"crossref","first-page":"26826","DOI":"10.18632\/oncotarget.5025","article-title":"Notch signaling deregulation in multiple myeloma: a rational molecular target","volume":"6","author":"Colombo","year":"2015","journal-title":"Oncotarget"},{"key":"10.1016\/j.bcp.2026.118518_b0150","doi-asserted-by":"crossref","first-page":"6402","DOI":"10.1128\/MCB.00299-08","article-title":"The association of Notch2 and NF-kappaB accelerates RANKL-induced osteoclastogenesis","volume":"28","author":"Fukushima","year":"2008","journal-title":"Mol. Cell Biol."},{"key":"10.1016\/j.bcp.2026.118518_b0155","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1126\/science.280.5372.2129","article-title":"Insecticidal toxins from the bacterium Photorhabdus luminescens","volume":"280","author":"Bowen","year":"1998","journal-title":"Science"},{"key":"10.1016\/j.bcp.2026.118518_b0160","doi-asserted-by":"crossref","first-page":"1250","DOI":"10.3390\/toxins2061250","article-title":"Toxins and secretion systems of Photorhabdus luminescens","volume":"2","author":"Rodou","year":"2010","journal-title":"Toxins"},{"key":"10.1016\/j.bcp.2026.118518_b0165","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1021\/cb100117k","article-title":"Exploiting a global regulator for small molecule discovery in Photorhabdus luminescens","volume":"5","author":"Kontnik","year":"2010","journal-title":"ACS Chem. Biol."},{"key":"10.1016\/j.bcp.2026.118518_b0170","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1128\/aem.54.6.1602-1605.1988","article-title":"Identification of an anthraquinone pigment and a hydroxystilbene antibiotic from Xenorhabdus luminescens","volume":"54","author":"Richardson","year":"1988","journal-title":"Appl. Environ. Microbiol."},{"key":"10.1016\/j.bcp.2026.118518_b0175","doi-asserted-by":"crossref","first-page":"e02577","DOI":"10.1128\/spectrum.02577-21","article-title":"Selective toxicity of secondary metabolites from the entomopathogenic bacterium Photorhabdus luminescens sonorensis against selected plant parasitic nematodes of the Tylenchina suborder","volume":"10","author":"Kusakabe","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"10.1016\/j.bcp.2026.118518_b0180","doi-asserted-by":"crossref","first-page":"616","DOI":"10.1038\/ja.2016.79","article-title":"Pyrazinone protease inhibitor metabolites from Photorhabdus luminescens","volume":"69","author":"Park","year":"2016","journal-title":"J. Antibiot."},{"key":"10.1016\/j.bcp.2026.118518_b0185","doi-asserted-by":"crossref","first-page":"3780","DOI":"10.1128\/AEM.68.8.3780-3789.2002","article-title":"Identification, characterization, and regulation of a cluster of genes involved in carbapenem biosynthesis in Photorhabdus luminescens","volume":"68","author":"Derzelle","year":"2002","journal-title":"Appl. Environ. Microbiol."},{"key":"10.1016\/j.bcp.2026.118518_b0190","doi-asserted-by":"crossref","first-page":"4387","DOI":"10.1007\/s00253-022-12023-9","article-title":"Natural products from Photorhabdus and Xenorhabdus: mechanisms and impacts","volume":"106","author":"Cimen","year":"2022","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"10.1016\/j.bcp.2026.118518_b0195","doi-asserted-by":"crossref","first-page":"4329","DOI":"10.1128\/aem.61.12.4329-4333.1995","article-title":"Identification of two pigments and a hydroxystilbene antibiotic from Photorhabdus luminescens","volume":"61","author":"Li","year":"1995","journal-title":"Appl. Environ. Microbiol."},{"key":"10.1016\/j.bcp.2026.118518_b0200","doi-asserted-by":"crossref","first-page":"1721","DOI":"10.1002\/cbic.200700300","article-title":"A type II polyketide synthase is responsible for anthraquinone biosynthesis in Photorhabdus luminescens","volume":"8","author":"Brachmann","year":"2007","journal-title":"Chembiochem"},{"key":"10.1016\/j.bcp.2026.118518_b0205","doi-asserted-by":"crossref","first-page":"12","DOI":"10.4014\/jmb.1708.08067","article-title":"Neuroprotective and anti-neuroinflammatory activities of anthraquinones isolated from Photorhabdus temperata culture broth","volume":"28","author":"Yang","year":"2018","journal-title":"J. Microbiol. Biotechnol."},{"key":"10.1016\/j.bcp.2026.118518_b0210","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1007\/s12272-024-01486-1","article-title":"New autophagy-modulating lanostane-type triterpenoids from a hallucinogenic poisonous mushroom Gymnopilus orientispectabilis","volume":"47","author":"Lee","year":"2024","journal-title":"Arch. Pharm. Res."},{"key":"10.1016\/j.bcp.2026.118518_b0215","doi-asserted-by":"crossref","first-page":"135","DOI":"10.20307\/nps.2024.30.2.135","article-title":"Phenolic compounds isolated from Juncus decipiens and their effects on osteoblast differentiation in the mouse mesenchymal stem cell line C3H10T1\/2","volume":"30","author":"Cho","year":"2024","journal-title":"Nat. Prod. Sci."},{"key":"10.1016\/j.bcp.2026.118518_b0220","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1007\/s12272-025-01553-1","article-title":"Activation of cryptic biosynthetic pathways in Saccharopolyspora spinosa through deletion of the spinosyn gene cluster: induction of cryptic and bioactive natural products","volume":"48","author":"Bridget","year":"2025","journal-title":"Arch. Pharm.. Res."},{"key":"10.1016\/j.bcp.2026.118518_b0225","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2023.115972","article-title":"1, 8-Dihydroxy-3-methoxy-anthraquinone inhibits tumor angiogenesis through HIF-1\u03b1 downregulation","volume":"220","author":"Hwang","year":"2024","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.bcp.2026.118518_b0230","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.bse.2003.11.006","article-title":"Chemistry and antifungal activity of Xyris species (Xyridaceae): a new anthraquinone from Xyris Pilosa","volume":"32","author":"Cota","year":"2004","journal-title":"Biochem. Syst. Ecol."},{"key":"10.1016\/j.bcp.2026.118518_b0235","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1038\/nature08878","article-title":"Therapeutic antibody targeting of individual Notch receptors","author":"Wu","year":"2010","journal-title":"Nature 464"},{"key":"10.1016\/j.bcp.2026.118518_b0240","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nsmb1227","article-title":"Structural basis for autoinhibition of Notch","volume":"14","author":"Gordon","year":"2007","journal-title":"Nat. Struct. Mol. Biol."},{"key":"10.1016\/j.bcp.2026.118518_b0245","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2021.101376","article-title":"Hairy and enhancer of split 1 is a primary effector of NOTCH2 signaling and induces osteoclast differentiation and function","volume":"297","author":"Yu","year":"2021","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bcp.2026.118518_b0250","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1091\/mbc.e02-07-0404","article-title":"IkappaBalpha and p65 regulate the cytoplasmic shuttling of nuclear corepressors: cross-talk between Notch and NFkappaB pathways","volume":"14","author":"Espinosa","year":"2003","journal-title":"Mol. Biol. Cell"},{"key":"10.1016\/j.bcp.2026.118518_b0255","doi-asserted-by":"crossref","DOI":"10.1016\/j.jbc.2023.105613","article-title":"NOTCH2 promotes osteoclast maturation and metabolism and modulates the transcriptome profile during osteoclastogenesis","volume":"300","author":"Canalis","year":"2024","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bcp.2026.118518_b0260","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1038\/19083","article-title":"presenilin-1-dependent gamma-secretase-like protease mediates release of Notch intracellular domain","volume":"398","author":"De Strooper","year":"1999","journal-title":"Nature"}],"container-title":["Biochemical Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295226008609?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0006295226008609?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T13:10:42Z","timestamp":1791810642000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0006295226008609"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":52,"alternative-id":["S0006295226008609"],"URL":"https:\/\/doi.org\/10.1016\/j.bcp.2026.118518","relation":{},"ISSN":["0006-2952"],"issn-type":[{"value":"0006-2952","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"3-Methoxychrysazin suppresses RANKL-induced osteoclastogenesis by modulating Notch2 signaling","name":"articletitle","label":"Article Title"},{"value":"Biochemical Pharmacology","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bcp.2026.118518","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"118518"}}