Human cGAS inhibitor
G140 | Unit size | Cat. code | Docs | Qty | Price |
---|---|---|---|---|---|
Human cGAS inhibitor |
2 mg |
inh-g140 |
Specific inhibitor of human cGAS
Inhibition of human cGAS signaling by G140
G140 is a small-molecule inhibitor of the double-stranded DNA (dsDNA) sensor, cGAS (cyclic GMP-AMP synthase; cGAMP synthase). G140 was identified in an in vitro high-throughput screen targeted towards recombinant human cGAS (hcGAS). Notably, G140, a pyrido-[4,3-b]-indole, features a methyl pyrazole group that significantly improves its potency and inhibitory activity against hcGAS [1].
cGAS is the primary sensor of cytosolic dsDNA, a danger signal indicating possible disturbances in homeostasis caused by infection, sterile tissue damage, and/or cancer. cGAS signals through STING and TBK1 to activate both the type I IFN and NF‑κB pathways [2,3].
Unlike RU.521, a previously developed murine cGAS inhibitor, G140 has been shown to specifically inhibit the activation of the hcGAS-induced type I IFN pathway [1]. G140 has been shown to have a dose-dependent inhibitory activity in both monocytes (i.e. THP1 cells) and primary human macrophages, with no off-target effects on a variety of different sensors [1]. Furthermore, G140 has been shown to exhibit inhibitory activity on cGAS-mediated activation of NF‑κB [1].
Key features of G140:
- G140 specifically inhibits human cGAS in a dose-dependent manner.
- G140 inhibits both cGAS-mediated IRF and NF-κB signaling.
- Each lot of G140 is highly pure (>95%) and functionally tested.
Please note: InvivoGen also offers the specific murine cGAS inhibitor RU.521
References:
1. Lama, L. et al. 2019. Development of human cGAS-specific small-molecule inhibitors for repression of dsDNA-triggered interferon expression. Nat Commun 10, 2261.
2. Gao, D. et al. 2015. Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases. PNAS 112, E5699-5705.
3. Abe, T. et al. 2014. Cytosolic-DNA-mediated, STINGdependent proinflammatory gene induction necessitates canonical NF-kappaB activation through TBK1. J Virol 88, 5328-5341.
Specifications
Formula: C17H16Cl2N4O2
Molecular weight: 379.24 g/mol
Solubility: 5 mg/ml (13.18 mM) in DMSO
Working concentration: 1 - 20 µM for cell culture assays.
Quality control:
- Purity ≥ 95% (UHPLC).
- Inhibition of cGAS has been confirmed using cellular assays
- The absence of bacterial contamination (e.g. lipoproteins and endotoxins) has been confirmed using HEK-Blue™ TLR2 and HEK‑Blue™ TLR4 cells.
Contents
- 2 mg G140 (provided as a dried powder)
G140 is shipped at room temperature.
Store at -20°C.
Resuspended product is stable for at least 6 months when properly stored.
Avoid repeated freeze-thaw cycles.