{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Chan P"],"funding":["Charlie Teo Foundation","Astellas Foundation for Research on Metabolic Disorders","NINDS NIH HHS","NCI NIH HHS","the NCI","Japan Society for the Promotion of Science","NINDS"],"pagination":["1772-1786"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12417823"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["27(7)"],"pubmed_abstract":["<h4>Background</h4>It has been reported that circadian clock components, Brain and Muscle ARNT-Like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), are essential for glioblastoma (GBM) stem cell (GSC) biology and survival. Consequently, we developed a novel Cryptochrome (CRY) activator SHP1705, which inhibits BMAL1-CLOCK transcriptional activity.<h4>Methods</h4>We utilized GlioVis to determine which circadian genes are differentially expressed in non-tumor versus GBM tissues. We employed in vitro and in vivo methods to test the efficacy of SHP1705 against patient-derived GSCs and xenografts in comparison to earlier CRY activator scaffolds. We applied a novel REV-ERB agonist SR29065, which inhibits BMAL1 transcription, to determine whether targeting both negative limbs of the"],"journal":["Neuro-oncology"],"pubmed_title":["Advancing clinical response against glioblastoma: Evaluating SHP1705 CRY2 activator efficacy in preclinical models and safety in phase I trials."],"pmcid":["PMC12417823"],"funding_grant_id":["R01 CA238662","F31 NS120654","24H00554","24H02266","21H04766"],"pubmed_authors":["Mkhitaryan S","Hirota T","Kay SA","Karapetyan G","Wu Q","Rich JN","Solt LA","Wang J","Cope J","Nagai Y","Kamenecka T","Chan P","Moats RA","Hovsepyan A"],"additional_accession":[]},"is_claimable":false,"name":"Advancing clinical response against glioblastoma: Evaluating SHP1705 CRY2 activator efficacy in preclinical models and safety in phase I trials.","description":"<h4>Background</h4>It has been reported that circadian clock components, Brain and Muscle ARNT-Like 1 (BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), are essential for glioblastoma (GBM) stem cell (GSC) biology and survival. Consequently, we developed a novel Cryptochrome (CRY) activator SHP1705, which inhibits BMAL1-CLOCK transcriptional activity.<h4>Methods</h4>We utilized GlioVis to determine which circadian genes are differentially expressed in non-tumor versus GBM tissues. We employed in vitro and in vivo methods to test the efficacy of SHP1705 against patient-derived GSCs and xenografts in comparison to earlier CRY activator scaffolds. We applied a novel REV-ERB agonist SR29065, which inhibits BMAL1 transcription, to determine whether targeting both negative limbs of the","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Sep","modification":"2026-06-02T01:03:07.718Z","creation":"2026-05-24T03:06:57.872Z"},"accession":"S-EPMC12417823","cross_references":{"pubmed":["40168112"],"doi":["10.1093/neuonc/noaf089"]}}