{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["14"],"submitter":["Saran U"],"pubmed_abstract":["Although breast cancer stem cells (BCSCs) are well characterized, molecularly targeting and eradicating this sub-population remains a challenge in the clinic. Recent studies have explored several signaling pathways that govern stem cell activation: We and others established that the Notch1 signaling plays a significant role in the proliferation, survival, and differentiation of BCSCs. Earlier, we reported that a newly developed small molecule, ASR490, binds to the negative regulatory region (NRR: The activation switch of the Notch receptor) of Notch1. <i>In vitro</i> results demonstrated that ASR490 significantly inhibited BCSCs (ALDH<sup>+</sup> and CD44<sup>+</sup>/CD24<sup>-</sup>) and breast cancer (BC) growth at nM concentrations, and subsequently inhibited the colony- and mammosphere-forming abilities of BCSCs and BCs. ASR490 downregulated the expressions of Notch1 intracellular domain (NICD: The active form of Notch1) and its downstream effectors Hey1 and HES1. Inhibition of Notch1-NICD facilitated autophagy-mediated growth inhibition by triggering the fusion of autophagosome and autolysosome in BCSCs. ASR490 was found to be non-toxic to healthy cells as compared to existing Notch1 inhibitors. Moreover, oral administration of ASR490 abrogated BCSC and BC tumor growth in the <i>in vivo</i> xenograft models. Together our results indicate that ASR490 is a potential therapeutic agent that inhibits BC tumor growth by targeting and abolishing Notch1 signaling in BCSCs and BC cells."],"journal":["Frontiers in pharmacology"],"pagination":["1150774"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9998682"],"repository":["biostudies-literature"],"pubmed_title":["A small molecule inhibitor of Notch1 modulates stemness and suppresses breast cancer cell growth."],"pmcid":["PMC9998682"],"pubmed_authors":["Shukla V","Tyagi A","Damodaran C","Chandrasekaran B","Saran U","Singh A","Sharma AK"],"additional_accession":[]},"is_claimable":false,"name":"A small molecule inhibitor of Notch1 modulates stemness and suppresses breast cancer cell growth.","description":"Although breast cancer stem cells (BCSCs) are well characterized, molecularly targeting and eradicating this sub-population remains a challenge in the clinic. Recent studies have explored several signaling pathways that govern stem cell activation: We and others established that the Notch1 signaling plays a significant role in the proliferation, survival, and differentiation of BCSCs. Earlier, we reported that a newly developed small molecule, ASR490, binds to the negative regulatory region (NRR: The activation switch of the Notch receptor) of Notch1. <i>In vitro</i> results demonstrated that ASR490 significantly inhibited BCSCs (ALDH<sup>+</sup> and CD44<sup>+</sup>/CD24<sup>-</sup>) and breast cancer (BC) growth at nM concentrations, and subsequently inhibited the colony- and mammosphere-forming abilities of BCSCs and BCs. ASR490 downregulated the expressions of Notch1 intracellular domain (NICD: The active form of Notch1) and its downstream effectors Hey1 and HES1. Inhibition of Notch1-NICD facilitated autophagy-mediated growth inhibition by triggering the fusion of autophagosome and autolysosome in BCSCs. ASR490 was found to be non-toxic to healthy cells as compared to existing Notch1 inhibitors. Moreover, oral administration of ASR490 abrogated BCSC and BC tumor growth in the <i>in vivo</i> xenograft models. Together our results indicate that ASR490 is a potential therapeutic agent that inhibits BC tumor growth by targeting and abolishing Notch1 signaling in BCSCs and BC cells.","dates":{"release":"2023-01-01T00:00:00Z","publication":"2023","modification":"2025-04-26T01:45:06.524Z","creation":"2025-04-06T10:11:49.755Z"},"accession":"S-EPMC9998682","cross_references":{"pubmed":["36909163"],"doi":["10.3389/fphar.2023.1150774"]}}