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Metabolite profiling of the stems of Tripterygium regelii using UPLC-qTOF-MS\/MS, combined with building block-based molecular networking (BBMN) analysis, led to the isolation of ten previously undescribed triterpene\u2212flavanol conjugates (1\u221210), including celastrol derivatives, as well as the annotation of 34 additional congeners sharing a similar core scaffold. The structures of compounds 1\u221210 were elucidated through comprehensive spectroscopic analyses, chemical derivatization, and quantum chemical calculations. All isolates exhibited configurationally stable sp3\u2212sp2 axial chirality at ambient temperature, and both P- and M-configured atropisomers were identified. In vitro evaluation of protein tyrosine phosphatase 1B (PTP1B) inhibition revealed that compound 10 exhibited potent activity, with an IC50 value of 0.6 \u00b1 0.1 \u03bcM, acting as a mixed-type inhibitor. These triterpene\u2212flavanol conjugates represent a new structural class with potential as lead compounds for the development of anti-obesity agents.<\/jats:p>","DOI":"10.1021\/acs.jnatprod.6c00683","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:02:52Z","timestamp":1787238172000},"page":"2536-2549","source":"Crossref","is-referenced-by-count":0,"title":["Building Block-Based Molecular Networking Enables Targeted Isolation of PTP1B-Inhibitory Triterpene\u2212Flavanol Conjugates from the Stems of\n                    <i>Tripterygium regelii<\/i>"],"prefix":"10.1021","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9058-7727","authenticated-orcid":true,"given":"Jorge-Eduardo","family":"Ponce-Zea","sequence":"first","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5077-2899","authenticated-orcid":true,"given":"Van-Hieu","family":"Mai","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6613-3858","authenticated-orcid":true,"given":"Jae-Sang","family":"Park","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4047-0721","authenticated-orcid":true,"given":"Thi-Tuyet-Minh","family":"Le","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So-Yeon","family":"Park","sequence":"additional","affiliation":[{"name":"Ewha Womans University , , ,","place":["Seoul, Republic of Korea, 03760"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7538-8850","authenticated-orcid":true,"given":"Yun-Sil","family":"Lee","sequence":"additional","affiliation":[{"name":"Ewha Womans University , , ,","place":["Seoul, Republic of Korea, 03760"]},{"name":"Ewha Womans University , , ,","place":["Seoul, Republic of Korea, 03760"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0761-3064","authenticated-orcid":true,"given":"Won-Keun","family":"Oh","sequence":"additional","affiliation":[{"name":"Seoul National University , , ,","place":["Seoul, Republic of Korea, 08826"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,20]]},"reference":[{"issue":"20","key":"2026100909065458600_cit1","doi-asserted-by":"publisher","first-page":"8612","DOI":"10.1002\/ece3.3344","article-title":"Phylogeographic and phylogenetic analysis for Tripterygium species delimitation","volume":"7","author":"Ma","year":"2017","journal-title":"Ecol. 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