Advancing clinical response against glioblastoma: Evaluating SHP1705 CRY2 activator efficacy in preclinical models and safety in phase I trials.

ABSTRACT:

Background

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.

Methods

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

SUBMITTER: Chan P 

PROVIDER: S-EPMC12417823 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature