{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Wang DP"],"funding":["Shandong Province Major Scientific and Technological Innovation Project, Shandong Provincial Key Laboratory Platform Project, National Natural Science Foundation of China Major Project","Shandong Province Major Scientific and Technological Innovation Project","National Natural Science Foundation of China","National Natural Science Foundation of China Major Project"],"pagination":["218"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10141377"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["21(4)"],"pubmed_abstract":["The JAK/STAT3 signaling pathway is aberrantly hyperactivated in many cancers, promoting cell proliferation, survival, invasiveness, and metastasis. Thus, inhibitors targeting JAK/STAT3 have enormous potential for cancer treatment. Herein, we modified <b>aldisine</b> derivatives by introducing the isothiouronium group, which can improve the antitumor activity of the compounds. We performed a high-throughput screen of 3157 compounds and identified compounds <b>11a</b>, <b>11b</b>, and <b>11c</b>, which contain a pyrrole [2,3-c] azepine structure linked to an isothiouronium group through different lengths of carbon alkyl chains and significantly inhibited JAK/STAT3 activities. Further results showed that compound <b>11c</b> exhibited the optimal antiproliferative activity and was a pan-JAKs inhibitor capable of inhibiting constitutive and IL-6-induced STAT3 activation. In addition, compound <b>11c</b> influenced STAT3 downstream gene expression (Bcl-xl, C-Myc, and Cyclin D1) and induced the apoptosis of A549 and DU145 cells in a dose-dependent manner. The antitumor effects of <b>11c</b> were further demonstrated in an in vivo subcutaneous tumor xenograft experiment with DU145 cells. Taken together, we designed and synthesized a novel small molecule JAKs inhibitor targeting the JAK/STAT3 signaling pathway, which has predicted therapeutic potential for JAK/STAT3 overactivated cancer treatment."],"journal":["Marine drugs"],"pubmed_title":["A Novel Aldisine Derivative Exhibits Potential Antitumor Effects by Targeting JAK/STAT3 Signaling."],"pmcid":["PMC10141377"],"funding_grant_id":["81991525","(No. 2020CXGC010503), (No. 2021ZDSYS11), (81991522)","Grant No. 82073759","82073759","2021ZDSYS11","2020CXGC010503"],"pubmed_authors":["Wu LH","Wang DP","Zhao CY","He N","Zhang QY","Li R","Jiang T"],"additional_accession":[]},"is_claimable":false,"name":"A Novel Aldisine Derivative Exhibits Potential Antitumor Effects by Targeting JAK/STAT3 Signaling.","description":"The JAK/STAT3 signaling pathway is aberrantly hyperactivated in many cancers, promoting cell proliferation, survival, invasiveness, and metastasis. Thus, inhibitors targeting JAK/STAT3 have enormous potential for cancer treatment. Herein, we modified <b>aldisine</b> derivatives by introducing the isothiouronium group, which can improve the antitumor activity of the compounds. We performed a high-throughput screen of 3157 compounds and identified compounds <b>11a</b>, <b>11b</b>, and <b>11c</b>, which contain a pyrrole [2,3-c] azepine structure linked to an isothiouronium group through different lengths of carbon alkyl chains and significantly inhibited JAK/STAT3 activities. Further results showed that compound <b>11c</b> exhibited the optimal antiproliferative activity and was a pan-JAKs inhibitor capable of inhibiting constitutive and IL-6-induced STAT3 activation. In addition, compound <b>11c</b> influenced STAT3 downstream gene expression (Bcl-xl, C-Myc, and Cyclin D1) and induced the apoptosis of A549 and DU145 cells in a dose-dependent manner. The antitumor effects of <b>11c</b> were further demonstrated in an in vivo subcutaneous tumor xenograft experiment with DU145 cells. Taken together, we designed and synthesized a novel small molecule JAKs inhibitor targeting the JAK/STAT3 signaling pathway, which has predicted therapeutic potential for JAK/STAT3 overactivated cancer treatment.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Mar","modification":"2026-04-08T13:33:24.238Z","creation":"2025-02-19T04:46:05.087Z"},"accession":"S-EPMC10141377","cross_references":{"pubmed":["37103357"],"doi":["10.3390/md21040218"]}}