{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ahmed MS"],"funding":["NHLBI NIH HHS","NCI NIH HHS","NIGMS NIH HHS"],"pagination":["372-388"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11343477"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["3(3)"],"pubmed_abstract":["Targeting Meis1 and Hoxb13 transcriptional activity could be a viable therapeutic strategy for heart regeneration. In this study, we performd an in silico screening to identify FDA-approved drugs that can inhibit Meis1 and Hoxb13 transcriptional activity based on the resolved crystal structure of Meis1 and Hoxb13 bound to DNA. Paromomycin (Paro) and neomycin (Neo) induced proliferation of neonatal rat ventricular myocytes in vitro and displayed dose-dependent inhibition of Meis1 and Hoxb13 transcriptional activity by luciferase assay and disruption of DNA binding by electromobility shift assay. X-ray crystal structure revealed that both Paro and Neo bind to Meis1 near the Hoxb13-interacting domain. Administration of Paro-Neo combination in adult mice and in pigs after cardiac ischemia/reperfusion injury induced cardiomyocyte proliferation, improved left ventricular systolic function and decreased scar formation. Collectively, we identified FDA-approved drugs with therapeutic potential for induction of heart regeneration in mammals."],"journal":["Nature cardiovascular research"],"pubmed_title":["Identification of FDA-approved drugs that induce heart regeneration in mammals."],"pmcid":["PMC11343477"],"funding_grant_id":["P01 HL160488","R01 GM119336","R35 GM127390","P01 HL160476","R35 HL166563","R01 HL149137","R01 HL147276","R01 CA248736"],"pubmed_authors":["Zhang CC","Zhang J","Menendez-Montes I","Pei J","Xing C","Lou X","Farag A","Liu X","Liu Y","Dos Santos M","Wang P","Tomczyk M","Lam NT","Sadek HA","Grishin NV","Cui M","Walcott G","Elhelaly WM","Secco I","Giacca M","Tomchick DR","Nakada Y","Ahmed MS","Zentilin L","Hsu CC","Nguyen NUN","Thet S","Zaha D"],"additional_accession":[]},"is_claimable":false,"name":"Identification of FDA-approved drugs that induce heart regeneration in mammals.","description":"Targeting Meis1 and Hoxb13 transcriptional activity could be a viable therapeutic strategy for heart regeneration. In this study, we performd an in silico screening to identify FDA-approved drugs that can inhibit Meis1 and Hoxb13 transcriptional activity based on the resolved crystal structure of Meis1 and Hoxb13 bound to DNA. Paromomycin (Paro) and neomycin (Neo) induced proliferation of neonatal rat ventricular myocytes in vitro and displayed dose-dependent inhibition of Meis1 and Hoxb13 transcriptional activity by luciferase assay and disruption of DNA binding by electromobility shift assay. X-ray crystal structure revealed that both Paro and Neo bind to Meis1 near the Hoxb13-interacting domain. Administration of Paro-Neo combination in adult mice and in pigs after cardiac ischemia/reperfusion injury induced cardiomyocyte proliferation, improved left ventricular systolic function and decreased scar formation. Collectively, we identified FDA-approved drugs with therapeutic potential for induction of heart regeneration in mammals.","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 Mar","modification":"2024-11-21T10:55:32.269Z","creation":"2024-11-21T10:55:32.269Z"},"accession":"S-EPMC11343477","cross_references":{"pubmed":["39183959"],"doi":["10.1038/s44161-024-00450-y"]}}