biostudies-literatureWang ZNCATS NIH HHSNIGMS NIH HHSNIH HHS1640-1656https://www.ebi.ac.uk/biostudies/studies/S-EPMC11363328biostudies-literatureUnknown10(8)Glioblastoma (GBM) is the most aggressive and frequently occurring type of malignant brain tumor in adults. The initiation, progression, and recurrence of malignant tumors are known to be driven by a small subpopulation of cells known as tumor-initiating cells or cancer stem cells (CSCs). GBM CSCs play a pivotal role in orchestrating drug resistance and tumor relapse. As a prospective avenue for GBM intervention, the targeted suppression of GBM CSCs holds considerable promise. In this study, we found that rocaglates, compounds which are known to inhibit translation <i>via</i> targeting of the DEAD-box helicase eIF4A, exert a robust, dose-dependent cytotoxic impact on GBM CSCs with minimal killing of nonstem GBM cells. Subsequent optimization identified novel rocaglate derivatives (rocaglatACS central scienceIdentification of Rocaglate Acyl Sulfamides as Selective Inhibitors of Glioblastoma Stem Cells.PMC11363328R35 GM118173S10 OD028585S10 OD026807U01 TR002625Mishra AKThakare RPMalonia SKLi RChitale SHuang SPelletier JFan ACZhu LJGreen MRPorco JAWang ZGoldstein SIBrown LECencic RfalseIdentification of Rocaglate Acyl Sulfamides as Selective Inhibitors of Glioblastoma Stem Cells.Glioblastoma (GBM) is the most aggressive and frequently occurring type of malignant brain tumor in adults. The initiation, progression, and recurrence of malignant tumors are known to be driven by a small subpopulation of cells known as tumor-initiating cells or cancer stem cells (CSCs). GBM CSCs play a pivotal role in orchestrating drug resistance and tumor relapse. As a prospective avenue for GBM intervention, the targeted suppression of GBM CSCs holds considerable promise. In this study, we found that rocaglates, compounds which are known to inhibit translation <i>via</i> targeting of the DEAD-box helicase eIF4A, exert a robust, dose-dependent cytotoxic impact on GBM CSCs with minimal killing of nonstem GBM cells. Subsequent optimization identified novel rocaglate derivatives (rocaglat2024-01-01T00:00:00Z2024 Aug2026-06-02T22:03:07.8Z2025-04-05T12:31:35.828ZS-EPMC113633283922071110.1021/acscentsci.4c01073