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.
British journal of cancer, 96(8), 1223-1233 (2007-04-05)
The pentacyclic acridinium methosulfate salt RHPS4 induces the 3'single-stranded guanine-rich telomeric overhang to fold into a G-quadruplex structure. Stabilisation of the latter is incompatible with an attachment of telomerase to the telomere and thus G-quadruplex ligands can effectively inhibit both
Clinical cancer research : an official journal of the American Association for Cancer Research, 17(8), 2227-2236 (2011-03-01)
We previously reported that the G-quadruplex (G4) ligand RHPS4 potentiates the antitumor activity of camptothecins both in vitro and in tumor xenografts. The present study aims at investigating the mechanisms involved in this specific drug interaction. Combination index test was
The pentacyclic acridine RHPS4 is a highly potent and specific G-quadruplex (G4) ligand, which binds and stabilizes telomeric G4 leading to the block of the replication forks at telomeres and consequently to telomere dysfunctionalization. In turn, the cell recognizes unprotected
G-quadruplex DNA targeting alters class-switch recombination in B cells and attenuates allergic inflammation.
Zeinab Dalloul et al.
The Journal of allergy and clinical immunology, 142(4), 1352-1355 (2018-06-24)
PARP1 is activated at telomeres upon G4 stabilization: possible target for telomere-based therapy.
Our team of scientists has experience in all areas of research including Life Science, Material Science, Chemical Synthesis, Chromatography, Analytical and many others.
