Biochem/physiol Actions
G-quadruplex (G4)-targeting telomerase inhibitor with anti-cancer efficacy in cultures and in vivo.
RHPS4 is a pentacyclic acridine compound that exerts telomerase inhibitory activity (IC50 = 330 nM by TRAP assay) via targeting telomeric DNA G-quadruplex (G4) structure, causing alteration in the telomeric architecture and telomere dysfunction. RHPS4 induces cell cycle arrest and growth inhibition in cancer cultures in vitro(% GI/culture/time = 93%/21NT/15 days, 67%/A431/12 days, 91%/GM847/15 days; 200 nM replenish twice weekly) and exhibits anti-tumor efficacy in mice in vivo (10-15 mg/kg/d iv.). RHPS4 is also reproted to target mitochondrial DNA (mtDNA) G4 structures, perturbing mitochondrial genome replication, transcription processivity, and respiratory function.