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Through\n                    <jats:italic toggle=\"yes\">in silico<\/jats:italic>\n                    analyses, including target prediction, pathway enrichment, and molecular docking, four key proteins\u2014MET, ADORA2A, CDK5R1, and ADORA1\u2014were identified as critical regulators of tumor proliferation, metastasis, and drug resistance pathways (e.g., Semaphorin interactions and NTRK1 signaling). Molecular docking and dynamics simulations revealed strong binding affinities and structural stability between selected compounds and these targets, prioritizing ADORA1 as a promising therapeutic node. To validate these findings, we synthesized compound 3 via a two-step chemical route, yielding a white solid product with 63% overall efficiency. Structural characterization by High-Resolution Mass Spectrometry (HRMS) and\n                    <jats:sup>1<\/jats:sup>\n                    H Nuclear Magnetic Resonance (NMR) confirmed its identity.\n                    <jats:italic toggle=\"yes\">In vitro<\/jats:italic>\n                    inhibition assays demonstrated that compound 3 exhibited potent activity against ADORA1, with a mean Half-Maximal Inhibitory Concentration (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) of 0.23 nM\u2014approximately twofold more effective than the positive control antagonist Dipropylcyclopentylxanthine (DPCPX) (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 0.46 nM). These results highlight compound 3 as a promising lead compound for further development in GC therapy, with potential to modulate ADORA1-mediated signaling pathways.\n                  <\/jats:p>","DOI":"10.1177\/1540658x251372072","type":"journal-article","created":{"date-parts":[[2025,9,11]],"date-time":"2025-09-11T15:10:06Z","timestamp":1757603406000},"page":"149-164","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Precision Targeting in Gastric Cancer: AI-Driven Discovery of MET, ADORA2A, CDK5R1, and ADORA1"],"prefix":"10.1177","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6989-1348","authenticated-orcid":false,"given":"Tiantian","family":"Tuo","sequence":"first","affiliation":[{"name":"School of Pharmaceutical and Chemical Engineering, Yangling Vocational and Technical College, Yangling, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengchan","family":"Wang","sequence":"additional","affiliation":[{"name":"Hunan Vocational College of Science and Technology, Changsha, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2025,9,11]]},"reference":[{"issue":"3","key":"e_1_3_5_2_2","first-page":"e22182","article-title":"Design, synthesis, and bioactivity evaluation of clindamycin derivatives against multidrug","volume":"85","author":"Jia Y","year":"2024","unstructured":"Jia Y, , Zhang Y, , Zhu H, et al. 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