Phen-DC3

Phen-DC3 is a bisquinolinium G-quadruplex (G4) ligand. Phen-DC3 selectively binds to and stabilizes the hybrid quadruplex-duplex hybrid (QDH) derived from the PIM1 promoter. Phen-DC3 also binds to the c-myc promoter Pu24T G4 via extensive π-stacking, and induces polymerase stalling at α-synuclein DNA and RNA G4 sequences. Phen-DC3 Trifluoromethanesulfonate (HY-15594A) downregulates LPS (HY-D1056)-induced TNFRSF21, RIPK3 and p-MLKL in VECs, and ameliorates CLP-induced pulmonary vascular leakage in septic rats. Phen-DC3 can be used in studies related to neurodegenerative diseases and sepsis-associated vascular injury^[1][2][3][4]. In Vitro:Phen-DC3 (10 μM; 12 h) reduces the expression of TNFRSF21, enhances cell viability, decreases cell permeability, and inhibits the expression of necroptosis markers (p-MLKL, RIPK3) in lipopolysaccharide (LPS)-stimulated primary rat pulmonary vein vascular endothelial cells (VECs)^[4].
Phen-DC3 (20-60 μM; 24 h) selectively stabilizes the hybrid QDH conformations of SO7 and SO8 derived from the PIM1 oncogene, increasing their melting temperatures by 13.5°C and 14.2°C, respectively, at a 1:1 ratio, while exerting minimal stabilizing effects on the antiparallel QDH SO2^[1].
Phen-DC3 (0.1-0.5 mM; 24 h) binds rigidly and specifically to the Q-D linker region of the chimeric PIM1 QDH SO7 in a single well-defined conformation, a characteristic determined by high-resolution NMR spectroscopy^[1].
Phen-DC3 (1.5 mM) selectively binds to and stabilizes the heterozygous conformation of polymorphic PIM1 QDH SO8-F in vitro, shifting its conformational equilibrium from a 50:50 heterozygous/antiparallel mixture to a single heterozygous complex^[1].
Phen-DC3 induces differential changes in nucleotide accessibility in wild-type (WT) and single-nucleotide polymorphism (SNP) α-synuclein RNA sequences, with the strongest effect (6- to 8-fold change) observed in SNP-511 RNA^[2].
Phen-DC3 regulates the accessibility of guanine in the DNA sequences of wild-type (WT) and single nucleotide polymorphism (SNP) α-synuclein, reducing the accessibility of SNP-877, SNP-962 and SNP-875 DNA by approximately 2-fold, which indicates its G4-stabilizing activity^[2].
Phen-DC3 (9 equiv; under conditions supporting Taq polymerase activity at 37 °C) potently induces Taq polymerase stalling in all wild-type (WT) and single nucleotide polymorphism (SNP) α-synuclein DNA sequences, with the highest stalling activity observed in WT DNA (a 47.7-fold change relative to KCl) and a comparable activity in SNP-875 DNA (a 47.1-fold change)^[2].
Phen-DC3 (DNA/ligand ratio 1:0.5-1:2; NOESY mixing times 200-700 ms; 25 °C) forms a 1:1 complex with the Pu24T G-quadruplex in the human c-myc promoter via extensive π-stacking interactions with the 5'-terminal top G-quadruplex. This interaction increases the thermal stability of the G-quadruplex by approximately 12 °C and exhibits submicromolar to nanomolar binding affinity^[3]. In Vivo:Phen-DC3 (1 mg/kg; i.v.; single dose; 12 hours post-CLP) improves sepsis-induced pulmonary vascular leakage in adult Sprague-Dawley rats^[4].
Phen-DC3 (~100-140 μM; microinjection) selectively binds and stabilizes the hybrid conformation of PIM1 QDH within the intracellular environment of Xenopus laevis oocytes, overriding the native cellular preference for the antiparallel QDH form^[1].