{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Isaacs JT"],"funding":["NIEHS NIH HHS","U.S. Department of Defense","NCI NIH HHS","National Institutes of Health"],"pagination":["1470-1493"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC10559933"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["83(15)"],"pubmed_abstract":["<h4>Background</h4>The quinoline-3-carboxamide, Tasquinimod (TasQ), is orally active as a maintenance therapy with an on-target mechanism-of-action via allosteric binding to HDAC4. This prevents formation of the HDAC4/NCoR1/HDAC3 complex, disrupting HIF-1α transcriptional activation and repressing MEF-2 target genes needed for adaptive survival signaling in the compromised tumor micro environment. In phase 3 clinical testing against metastatic castration-resistant prostate cancer(mCRPC), TasQ (1 mg/day) increased time-to-progression, but not overall survival.<h4>Methods</h4>TasQ analogs were chemically synthesized and tested for activity compared to the parental compound. These included HDAC4 enzymatic assays, qRT-PCR and western blot analyses of gene and protein expression following treat"],"journal":["The Prostate"],"pubmed_title":["Third generation quinoline-3-carboxamide transcriptional disrupter of HDAC4, HIF-1α, and MEF-2 signaling for metastatic castration-resistant prostate cancer."],"pmcid":["PMC10559933"],"funding_grant_id":["P30 CA006973","R01 CA255259","P50 CA058236","R35 ES028244"],"pubmed_authors":["Perdew GH","Kostova M","Antony L","Murray IA","Isaacs JT","Dalrymple SL","Denmeade SR","Brennen WN","Nelson PS","Marc Rosen D","Akinboye ES","Coleman IM"],"additional_accession":[]},"is_claimable":false,"name":"Third generation quinoline-3-carboxamide transcriptional disrupter of HDAC4, HIF-1α, and MEF-2 signaling for metastatic castration-resistant prostate cancer.","description":"<h4>Background</h4>The quinoline-3-carboxamide, Tasquinimod (TasQ), is orally active as a maintenance therapy with an on-target mechanism-of-action via allosteric binding to HDAC4. This prevents formation of the HDAC4/NCoR1/HDAC3 complex, disrupting HIF-1α transcriptional activation and repressing MEF-2 target genes needed for adaptive survival signaling in the compromised tumor micro environment. In phase 3 clinical testing against metastatic castration-resistant prostate cancer(mCRPC), TasQ (1 mg/day) increased time-to-progression, but not overall survival.<h4>Methods</h4>TasQ analogs were chemically synthesized and tested for activity compared to the parental compound. These included HDAC4 enzymatic assays, qRT-PCR and western blot analyses of gene and protein expression following treat","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023 Nov","modification":"2026-04-08T18:37:00.851Z","creation":"2025-04-06T14:23:50.11Z"},"accession":"S-EPMC10559933","cross_references":{"pubmed":["37559436"],"doi":["10.1002/pros.24606"]}}