RHPS4

RHPS4 (3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate) is a pentacyclic acridine derivative that acts as a potent G-quadruplex (G4) DNA stabilizer and telomerase inhibitor. Originally developed at the University of Nottingham and licensed by Pharminox, RHPS4 binds to and stabilizes G-quadruplex structures, particularly at telomeres, leading to telomere uncapping, DNA damage response activation, and cell cycle arrest. It has been extensively studied in preclinical models for its antitumor activity, both as a monotherapy and in combination with chemotherapeutics or radiotherapy. However, its clinical development was halted due to off-target cardiotoxicity, including hERG channel inhibition and interactions with adrenergic and muscarinic receptors. More recently, RHPS4 has also been investigated for its ability to target mitochondrial G-quadruplexes, disrupting mitochondrial DNA replication and transcription, which has shown promise in models of renal proximal tubule cell dysfunction and as an antimalarial strategy against *Plasmodium falciparum*.

Other names

3,11-difluoro-6,8,13-trimethyl-8H-quino[4,3,2-kl]acridinium methosulfate3,11-difluoro-6,8,13-trimethylquino[4,3,2-kl]acridinium methylsulfateRHPS 4RHPS4RHPS-4RHPS 4 methosulfateRHPS4 methosulfateRHPS-4 methosulfateRHPS4 methyl sulfateRHPS-4 methyl sulfateRHPS 4 methyl sulfateRHPS4 methylsulfateRHPS-4 methylsulfateRHPS 4 methylsulfate