Telomeric G4s ligand 1 is a telomere G-quadruplex ligand that stabilizes telomeric G4 structures and induces the formation of R-loops, leading to DNA damage responses. It prompts apoptosis in tumor cells and triggers immunogenic cell death (ICD).

Telomeric G4s ligand 1 (compound R1; 1-4 μM; 24 hours) enhances the stability of G4 structures and induces the formation of R loops in the telomeric regions of MDA-MB-231 cells, triggering DNA damage responses, G2/M cell cycle arrest, apoptosis, and exhibiting antiproliferative effects. Additionally, Telomeric G4s ligand 1 stimulates immunogenic cell death (ICD) in tumor cells, thereby promoting the maturation of bone marrow-derived dendritic cells (BMDC). Treatment with 1 μM, 2 μM, and 4 μM concentrations over 24 hours increased levels of DNA damage-related proteins, including γH2AX and replication protein A subunit.

The compound Telomeric G4s ligand 1 (compound R1; 10 mg/kg; intraperitoneal injection; every other day for 14 days) significantly reduces tumor burden through immunomodulatory effects, evidenced by an increase in CD4+ and CD8+ T cells within tumors and elevated cytokine levels in the serum in a breast cancer mouse model.