{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T10:28:04Z","timestamp":1785234484366,"version":"3.55.0"},"reference-count":78,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T00:00:00Z","timestamp":1745452800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Crohn\u2019s disease is an inflammatory bowel disease (IBD) that currently lacks satisfactory treatment options. Therefore, new targets for new drugs are urgently needed to combat this disease. In the present study, we investigated the transcriptomics-based mRNA expression of intestinal biopsies from patients with Crohn\u2019s disease. We compared the mRNA expression profiles of the ileum and colon of patients with those of healthy individuals. A total of 72 genes in the ileum and 33 genes in the colon were differentially regulated. Among these, six genes were overexpressed in both tissues, including IL1B, TCL1A, HCAR3, IGHG1, S100AB, and OSM. We further focused on OSM\/oncostatin M. To confirm the responsiveness of intestinal tissues from patients with Crohn\u2019s disease to oncostatin M inhibition, we examined the expression of the oncostatin M using immunohistochemistry in patient biopsies as well as in kindlin-1\u2212\/\u2212 and kindlin-2\u2212\/\u2212 knockout mice, which exhibit an inflammatory bowel disease (IBD) phenotype, and found strong oncostatin M expression in all samples examined. Next, we conducted a drug-repurposing study using the supercomputer MOGON and bioinformatic methods. A total of 13 candidate compounds out of 1577 FDA-approved drugs were identified by PyRx-based virtual drug screening and AutoDock-based molecular docking. Their lowest binding energies (LBEs) ranged from \u221210.46 (\u00b10.08) to \u22128.77 (\u00b10.08) kcal\/mol, and their predicted inhibition constants (pKi) ranged from 21.62 (\u00b12.97) to 373.78 (\u00b136.78) nM. Ecamsule has an interesting stereostructure with two C2-symmetric enantiomers (1S,4R-1\u2032S,4\u2032R and 1R,4S-1\u2032R,4\u2032S) (1a and 1b) and one meso diastereomer (1S,4R-1\u2032R,4\u2032S) (1c). These three stereoisomers showed strong, albeit differing, binding affinities in molecular docking. As examined by nuclear magnetic resonance and polarimetry, the 1S,4R-1\u2032S,4\u2032R isomer was the stereoisomer present in our commercially available preparations used for microscale thermophoresis. Ecamsule (1a) was chosen for in vitro validation using recombinant oncostatin M and microscale thermophoresis. Considerable dissociation constants were obtained for ecamsule after three repetitions with a Kd value of 11.36 \u00b1 2.83 \u00b5M. Subsequently, we evaluated, by qRT-PCR, the efficacy of ecamsule (1a) as a potential drug that could prevent oncostatin M activation by inhibiting downstream inflammatory marker genes (IL6, TNFA, and CXCL11). In conclusion, we have identified oncostatin M as a promising new drug target for Crohn\u2019s disease through transcriptomics and ecamsule as a potential new drug candidate for Crohn\u2019s disease through a drug-repurposing approach both in silico and in vitro.<\/jats:p>","DOI":"10.3390\/molecules30091897","type":"journal-article","created":{"date-parts":[[2025,4,24]],"date-time":"2025-04-24T09:26:58Z","timestamp":1745486818000},"page":"1897","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Drug Repurposing to Inhibit Oncostatin M in Crohn\u2019s Disease"],"prefix":"10.3390","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-1845-586X","authenticated-orcid":false,"given":"Faranak","family":"Bahramimehr","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Axel","family":"Guthart","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kurz","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1709-6996","authenticated-orcid":false,"given":"Yuanping","family":"Hai","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Dawood","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"},{"name":"Department of Molecular Biology, Faculty of Medical Laboratory Science, Al-Neelain University, Khartoum 11121, Sudan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9678-3323","authenticated-orcid":false,"given":"R\u00fcmeysa","family":"Y\u00fccer","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9454-3599","authenticated-orcid":false,"given":"Nasim","family":"Shahhamzehei","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3888-0931","authenticated-orcid":false,"given":"Ralf","family":"Weiskirchen","sequence":"additional","affiliation":[{"name":"Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, 52074 Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wilfried","family":"Roth","sequence":"additional","affiliation":[{"name":"Institute of Pathology, University Medical Center, Johannes Gutenberg University, 55131 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8545-1753","authenticated-orcid":false,"given":"Wolfgang","family":"Stremmel","sequence":"additional","affiliation":[{"name":"Clinic for Internal Medicine, Beethovenstra\u00dfe 2, 76530 Baden-Baden, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3583-5935","authenticated-orcid":false,"given":"Gerhard","family":"Bringmann","sequence":"additional","affiliation":[{"name":"Institute of Organic Chemistry, University of W\u00fcrzburg, Am Hubland, 97074 W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2637-1681","authenticated-orcid":false,"given":"Thomas","family":"Efferth","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"370","DOI":"10.1136\/archdischild-2023-325668","article-title":"Inflammatory Bowel Disease: Recent Developments","volume":"109","author":"Ashton","year":"2024","journal-title":"Arch. 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