Cyclic GMP-AMP Synthase Inhibitor

RU.521 (RU320521) is a potent and selective cyclic GMP-AMP synthase (cGAS) inhibitor and inhibits cGAS-mediated interferon upregulation. RU.521 suppresses dsDNA-activated reporter activity with an IC₅₀ of 0.7 μM. RU.521 reduces constitutive expression of interferon in macrophages from a mouse model of Aicardi-Goutières syndrome (AGS).

G140 is a potent and selective inhibitor of cyclic GMP-AMP synthase (cGAS), with IC₅₀s of 14.0 nM and 442 nM for h-cGAS and m-cGAS, respectively. G140 has anti-inflammatory activity.

G150 is a highly selective human cyclic GMP-AMP synthase (h-cGAS) inhibitor with an IC₅₀ of 10.2 nM. G150 represses dsDNA-triggered interferon expression, and G150 can be used for the research of inflammatory.

PF-06928215 is a cGAS (cyclic GMP-AMP Synthase) inhibitor with an IC₅₀ of 4.9 μΜ. PF-06928215 has a high binding affinity of 0.2 μM (K_d).

Decoyinine is a selective inhibitor of GMP synthetase (GMPS).

Iptocigistat (Iptocigistatum) is a cyclic GMP-AMP synthase (cGAS) inhibitor. Iptocigistat prevents excessive immune responses. Iptocigistat can be used to study inflammation-related autoimmune diseases.

cGAS-IN-2 (compound 109) is a potent inhibitor of Cyclic GMP-AMP Synthase (cGAS), with IC₅₀ of 0.01512 μM for h-cGAS.

XQ2B is a specific cGAS inhibitor targeting protein-DNA interaction and phase separation. XQ2B markedly reduces ISD-induced Autophagy. XQ2B inhibits herpes simplex virus 1 (HSV-1)-induced antiviral immune responses and enhances HSV-1 infection.

cGAS-IN-1 (Compound C20) is a cyclic GMP-AMP synthase (cGAS) inhibitor with IC₅₀s of 2.28 μM (human cGAS, h-cGAS^FL) and 1.44 μM (mouse cGAS, m-cGAS^CD). cGAS-IN-1 can be used for the studies of autoimmune diseases and chronic inflammation.

TDI-6570 (TDI-006570) is a blood-brain barrier-permeable, orally active cGAS inhibitor with an IC₅₀ of 1.64 μM. TDI-6570 exhibits high gastrointestinal absorption and a long brain half-life in mice, and shows no toxicity to primary neurons. By inhibiting the cGAS-STING-IFN signaling pathway, TDI-6570 reduces STING levels and the activation of TBK1, blocks double-stranded DNA-induced cGAS activation and downstream interferon-stimulated gene expression, thereby reducing tau protein spread and improving synaptic loss. TDI-6570 reverses memory deficits, increases the amplitude of long-term potentiation, enhances the MEF2C transcriptional network, restores PSD-95 and vGAT punctate structures, and significantly improves cognitive resilience. TDI-6570 can be applied to the research of Alzheimer's disease, Parkinson's disease, systemic lupus erythematosus, as well as various central nervous system and autoimmune diseases.

IRAK4-IN-4 (Compound 15) is an interleukin-1 receptor-associated kinase 4 (IRAK4) inhibitor, with an IC₅₀ of 2.8 nM. IRAK4-IN-4 also inhibits cyclic GMP-AMP synthase (cGAS) with an IC₅₀ of 2.1 nM. IRAK4-IN-4 can be used for research of autoimmune diseases.

cGAS-IN-4 (Compound 36) is an orally active inhibitor for cyclic GMP-AMP synthase (cGAS) with IC₅₀ of 32 nM and 5.8 nM for h-cGAS and m-cGAS. cGAS-IN-4 inhibits the cGAMP in THP-1 cell with an IC₅₀ of 60 nM, which improves the cellular potency. cGAS-IN-4 exhibits anti-inflammatory efficacy in Concanavalin A (HY-P2149)-induced acute liver injury in mouse models. orally active, THP-1, C57Bl/6 mouse, orally active

XL-3156 is a cGAS inhibitor. XL-3156 occupies both allosteric and orthosteric sites simultaneously, and inhibits the interaction and phase separation between cGAS and DNA by stabilizing the closed conformation of the activation loop. XL-3156 can be used in the research of diseases such as autoimmune diseases and inflammation.

LYPLAL1-IN-1 (compound 11) is a selective, covalent, and irreversible inhibitor of the lysophospholipase-like enzyme LYPLAL1 (IC₅₀ = 6 nM). LYPLAL1-IN-1 shows selectivity against other serine hydrolases such as carboxylesterase CES1 (IC₅₀ > 50 μM for CES1). LYPLAL1-IN-1 inhibits the depalmitoylation function of LYPLAL1, blocking its depalmitoylation modification of cyclic GMP-AMP synthase (cGAS), thereby promoting cGAS dimerization and activation, and initiating the cGAS-STING pathway-mediated innate immune response. LYPLAL1-IN-1 can enhance DNA-induced type I interferon production, upregulate PD-L1 expression in tumor cells, and promote the accumulation of tumor-infiltrating CD8⁺ T cells, with the core function of strengthening the anti-tumor immune response. LYPLAL1-IN-1 is primarily used in tumor immunology research, especially in combination with PD-1/PD-L1 inhibitors.

XL-3158 is a selective and cross-species Cyclic GMP-AMP synthase (cGAS) inhibitor (IC₅₀: 11.1 μM for human cGAS, 2.19 μM for mouse cGAS). XL-3158 simultaneously occupy allosteric and orthosteric sites, stabilizing the activation loop in a closed, inactive conformation and thereby attenuating the cGAS-DNA interactions. XL-3158 inhibits cGAS by targeting phase separation. XL-3158 efficiently penetrates cells by inhibiting aggregate formation, effectively reducing the local concentration of cGAS within cells. XL-3158 can be used for the study of cGAS-dependent inflammatory diseases.

HA-1004 is a selective inhibitor of PKA, which can inhibit lipolysis and induce vascular relaxation. HA-1004 is also a dual inhibitor of cyclic GMP-dependent protein kinase and cyclic AMP-dependent protein, and is involved in smooth muscle, second messenger, cyclic AMP and cyclic GMP regulation mechanisms. HA-1004 is an antagonist for calcium, that can be used as a vasodilator to inhibit the contraction of rabbit aortic strips, or to antagonize ERK and tyrosine hydroxylase (TH) phosphorylation in morphine abstinence rat models.

CU-32 is a potent cGAS inhibitor with an IC₅₀ of 0.45 µM. CU-32 decreases IFN-stimulatory DNA-induced production of IFN-β in THP-1 cells.

CU-76 is an inhibitor for human cyclic GMP-AMP synthase (hcGAS) with an IC₅₀ of 0.24 μM. CU-76 selectively inhibits the DNA pathway in human cells, and can be used in autoimmune research.

cGAS-IN-8 is an indazole cyclic GMP-AMP synthase (cGAS) inhibitor with an IC₅₀ of 6 nM for human cGAS. cGAS-IN-8 inhibits cGAMP production in THP-1 cells with an IC₅₀ of 0.12 µM. cGAS-IN-8 does not inhibits hERG activity. cGAS-IN-8 can be used for the research of autoimmune diseases.

HA-1004 hydrochloride is a selective inhibitor of PKA, which can inhibit lipolysis and induce vascular relaxation. HA-1004 hydrochloride is also a dual inhibitor of cyclic GMP-dependent protein kinase and cyclic AMP-dependent protein (Cyclic GMP-AMP Synthase), and is involved in smooth muscle, second messenger, cyclic AMP and cyclic GMP regulation mechanisms. HA-1004 hydrochloride an antagonist for calcium, that can be used as a vasodilator to inhibit the contraction of rabbit aortic strips, or to antagonize ERK and tyrosine hydroxylase (TH) phosphorylation in morphine abstinence rat models.