{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T03:27:26Z","timestamp":1760239646167,"version":"build-2065373602"},"reference-count":21,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T00:00:00Z","timestamp":1606694400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K15134"],"award-info":[{"award-number":["16K15134"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Marine Drugs"],"abstract":"<jats:p>Fibrodysplasia ossificans progressiva (FOP) is a rare congenital disorder with heterotopic ossification (HO) in soft tissues. The abnormal activation of bone morphogenetic protein (BMP) signaling by a mutant activin receptor-like kinase-2 (ALK2) leads to the development of HO in FOP patients, and, thus, BMP signaling inhibitors are promising therapeutic applications for FOP. In the present study, we screened extracts of 188 Indonesian marine invertebrates for small molecular inhibitors of BMP-induced alkaline phosphatase (ALP) activity, a marker of osteoblastic differentiation in a C2C12 cell line stably expressing ALK2(R206H) (C2C12(R206H) cells), and identified five marine sponges with potent ALP inhibitory activities. The activity-guided purification of an EtOH extract of marine sponge Dysidea sp. (No. 256) resulted in the isolation of dysidenin (1), herbasterol (2), and stellettasterol (3) as active components. Compounds 1\u20133 inhibited ALP activity in C2C12(R206H) cells with IC50 values of 2.3, 4.3, and 4.2 \u00b5M, respectively, without any cytotoxicity, even at 18.4\u201321.4 \u00b5M. The direct effects of BMP signaling examined using the Id1WT4F-luciferase reporter assay showed that compounds 1\u20133 did not decrease the reporter activity, suggesting that they inhibit the downstream of the Smad transcriptional step in BMP signaling.<\/jats:p>","DOI":"10.3390\/md18120606","type":"journal-article","created":{"date-parts":[[2020,11,30]],"date-time":"2020-11-30T10:26:12Z","timestamp":1606731972000},"page":"606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Screening for Small Molecule Inhibitors of BMP-Induced Osteoblastic Differentiation from Indonesian Marine Invertebrates"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1540-7255","authenticated-orcid":false,"given":"Hiroyuki","family":"Yamazaki","sequence":"first","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Satoshi","family":"Ohte","sequence":"additional","affiliation":[{"name":"Graduate School of Pharmaceutical Sciences, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henki","family":"Rotinsulu","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan"},{"name":"Faculty of Mathematic and Natural Sciences, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Defny S.","family":"Wewengkang","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan"},{"name":"Faculty of Mathematic and Natural Sciences, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9942-7001","authenticated-orcid":false,"given":"Deiske A.","family":"Sumilat","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan"},{"name":"Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Delfly B.","family":"Abdjul","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan"},{"name":"Faculty of Fisheries and Marine Science, Sam Ratulangi University, Kampus Bahu, Manado 95115, Indonesia"},{"name":"North Sulawesi Research and Development Agency, 17 Agustus Street, Manado 95117, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wilmar","family":"Maarisit","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, Japan"},{"name":"Faculty of Mathematics and Natural Sciences, Indonesia Christian University, Tomohon 95362, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Magie M.","family":"Kapojos","sequence":"additional","affiliation":[{"name":"Faculty of Nursing, University of Pembangunan Indonesia, Bahu, Manado 95115, Indonesia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michio","family":"Namikoshi","sequence":"additional","affiliation":[{"name":"Faculty of Pharmaceutical Sciences, Tohoku Medical and Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai 981-8558, 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