Cyclic GMP-AMP Synthase Activator

Telomeric G4s ligand 2 is an orally active, selective ligand of telomeric G-quadruplex (G4), with an IC₅₀ of 0.4 μM. Telomeric G4s ligand 2 binds to dimeric telomeric G4, inhibits the activities of DHX36 and BLM helicases. Telomeric G4s ligand 2 activates cGAS-STING and TERRA-ZBP1 pathways, inducing autophagy and G2/M cell cycle arrest, and exhibits antiproliferative effects across cancer cell lines. Telomeric G4s ligand 2 can be used for the study of colorectal cancer.

Poly(deoxyadenylic-thymidylic) acid (Poly(dA:dT)) sodium is a double-stranded DNA stimulant. Poly(deoxyadenylic-thymidylic) acid sodium is recognized by the intracellular DNA sensor DDX41 and activates the innate immune pathway via the adaptor protein STING, inducing the production of cytokines such as type I interferons. Poly(deoxyadenylic-thymidylic) acid sodium also serves as an in vitro transcription template for free RNA polymerase.

QKY-613 is a prodrug that enhances immune surveillance by targeting nucleic acid modification pathways. QKY-613 promotes the selective incorporation of 6mdA (N6-methyldeoxyadenosine) into viral DNA, enhancing the phase separation potential of DNA, thereby increasing the activation of cGAS and strengthening host immune surveillance. In virus-infected mouse models, QKY-613 significantly reduced mortality in aged mice. QKY-613 holds promise for research on nucleic acid modification-based immune surveillance mechanisms.

Ferroptosis inducer-17 is a ferroptosis inducer that downregulates GPX4 and activates the CTSB and cGAS-STING pathways. Ferroptosis inducer-17 exhibits cytotoxicity against cancer cells but low toxicity toward normal cells. Ferroptosis inducer-17 accumulates in mitochondria and lysosomes, thereby inducing ROS production, lipid peroxidation, mitochondrial membrane depolarization, lysosomal iron accumulation, increased membrane permeability, and enhanced oxidative stress. Ferroptosis inducer-17 inhibits tumor growth in cisplatin-resistant xenograft models. Ferroptosis inducer-17 can be used for cancer-related research.