{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Ota Y"],"funding":["Japan Agency for Medical Research and Development","Ministry of Education, Culture, Sports, Science and Technology","Uehara Memorial Foundation"],"pagination":["1568-1573"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9575174"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["13(10)"],"pubmed_abstract":["Anticancer drug delivery by small molecules offers a number of advantages over conventional macromolecular drug delivery systems. We previously developed phenylcyclopropylamine (PCPA)-drug conjugates (PDCs) as small-molecule-based drug delivery vehicles for targeting lysine-specific demethylase 1 (LSD1)-overexpressing cancers. In this study, we applied this PDC strategy to the HDAC-inhibitory anticancer agent vorinostat. Among three synthesized PCPA or arylcyclopropylamine (ACPA)-vorinostat conjugates <b>1</b>, <b>9</b>, and <b>32</b>, conjugate <b>32</b> with a 4-oxybenzyl linker showed sufficient stability in buffer solutions, potent LSD1 inhibition, efficient LSD1-dependent vorinostat release, and potent and selective antiproliferative activity toward LSD1-expressing human breast cancer and small-cell lung cancer cell lines. These results indicate that the conjugate selectively releases vorinostat in cancer cells. A similar strategy may be applicable to other anticancer drugs."],"journal":["ACS medicinal chemistry letters"],"pubmed_title":["Cancer-Cell-Selective Targeting by Arylcyclopropylamine-Vorinostat Conjugates."],"pmcid":["PMC9575174"],"funding_grant_id":["JP22ama121041","JPMJCR14L2"],"pubmed_authors":["Elboray EE","Takada Y","Suzuki T","Sakai T","Morita M","Sowa Y","Kurohara T","Mukherjee A","Zamani F","Hu C","Horinaka M","Yamashita Y","Masuda M","Itoh Y","Ota Y","Singh R"],"additional_accession":[]},"is_claimable":false,"name":"Cancer-Cell-Selective Targeting by Arylcyclopropylamine-Vorinostat Conjugates.","description":"Anticancer drug delivery by small molecules offers a number of advantages over conventional macromolecular drug delivery systems. We previously developed phenylcyclopropylamine (PCPA)-drug conjugates (PDCs) as small-molecule-based drug delivery vehicles for targeting lysine-specific demethylase 1 (LSD1)-overexpressing cancers. In this study, we applied this PDC strategy to the HDAC-inhibitory anticancer agent vorinostat. Among three synthesized PCPA or arylcyclopropylamine (ACPA)-vorinostat conjugates <b>1</b>, <b>9</b>, and <b>32</b>, conjugate <b>32</b> with a 4-oxybenzyl linker showed sufficient stability in buffer solutions, potent LSD1 inhibition, efficient LSD1-dependent vorinostat release, and potent and selective antiproliferative activity toward LSD1-expressing human breast cancer and small-cell lung cancer cell lines. These results indicate that the conjugate selectively releases vorinostat in cancer cells. A similar strategy may be applicable to other anticancer drugs.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Oct","modification":"2024-11-14T19:20:25.441Z","creation":"2024-11-14T19:20:25.441Z"},"accession":"S-EPMC9575174","cross_references":{"pubmed":["36262394"],"doi":["10.1021/acsmedchemlett.2c00126"]}}