TDI-6570
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Cat.code:
inh-tdi6570-1
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ABOUT
Specific inhibitor of mouse cGAS
TDI-6570 is described as a small molecule inhibitor of the murine cytosolic double-stranded (ds)DNA sensor cyclic GMP-AMP synthase (cGAS) [1]. cGAS is the primary sensor of cytosolic dsDNA, a danger signal indicating possible disturbances in homeostasis caused by infection, sterile tissue damage, or cancer [1-3].
Mode of action
In a healthy individual, cGAS senses the abnormal presence of cytosolic DNA in the context of infection. In diseases, cGAS hyperactivation promotes deleterious type I IFN responses and therefore drives neurodegenerative diseases [2]. TDI-6570 is described as one of the most potent inhibitors for mouse cGAS [3]. It possesses high gastrointestinal absorption and good brain permeability [1-2]. TDI-6570 has been used to determine the effects of cGAS inhibition on the cGAS-STING pathway in a mouse model of tauopathy (Alzheimer's disease (AD)) [1]. Even high concentrations of TDI-6570 show no substantial toxicity [1]. TDI-6570 can be formulated into chow diet and is orally administrable [1-2]. Inhibition of cGAS using TDI-6570 represents a promising therapeutic strategy to treat multiple neurodegenerative diseases, including AD, Huntington's, or Parkinson's disease [3].
InvivoGen's TDI-6570 efficiently inhibits mouse cGAS, but not human cGAS, as assessed using InvivoGen's reporter cell lines J774-Dual™ and THP1-Dual™, respectively (see figures).
Key features of TDI-6570
- Potent and specific inhibitor of mouse cGAS
- No substantial toxicity in vivo [1]
- Orally administrable in mice [1]
- InvitroFit™ grade: each lot is highly pure (≥95%) and functionally tested.
References:
1. Lo I, et al. 2023. Tau activation of microglial cGAS-IFN reduces MEF2C-mediated cognitive resilience. Nat Neurosci. 26(5):737-750.
2. Lama L, et al. 2019. Development of human cGAS-specific small-molecule inhibitors for repression of dsDNA-triggered interferon expression. Nat Commun.10(1):2261.
3. Huang Y, et al. 2023. . Mechanism and therapeutic potential of targeting cGAS-STING signaling in neurological disorders. Mol Neurodegener.18(1):79.
All products are for research use only, and not for human or veterinary use.
InvitroFit™
InvitroFit™ is a high-quality standard specifically adapted for in vitro studies of inhibitors. InvitroFit™ products are highly pure (≥95%) and guaranteed free of bacterial contamination, as confirmed using HEK Blue™ TLR2 and HEK Blue™ TLR4 cellular assays. Each lot is rigorously tested for functional activity using validated (or proprietary) cellular models. This grade ensures reliability and reproducibility for your research applications.
SPECIFICATIONS
Specifications
C14H14CIFN2O2
5 mg/ml in DMSO. Product may require heating to 37°C for complete dissolution
0.01 - 1 µM (depending on the agonist; see VDS for more details)
Negative (tested using EndotoxDetect™ assay)
In vitro cellular assays
Each lot is functionally tested and validated using cellular assays.
CONTENTS
Contents
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Product:TDI-6570
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Cat code:inh-tdi6570-1
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Quantity:2 mg
TDI-6570 is provided as a translucent film.
Shipping & Storage
- Shipping method: Room temperature
- -20°C
- Avoid repeated freeze-thaw cycles
Storage:
Caution:
Details
cGAS - Cyclic GMP-AMP synthase
Cyclic GMP-AMP synthase (cGAS, cGAMP synthase) is a critical cytosolic DNA sensor that triggers innate immune responses through the production of type I interferons (IFNs) [1]. In response to cytosolic double‑stranded DNA (dsDNA), cGAS produces the cyclic dinucleotide (CDN) 2’3’-cGAMP.
CDNs bind directly to STING, leading to TBK1‑IRF3-mediated activation of IFN-stimulated response elements (ISRE) in the promoters of IFN-stimulated genes (ISG). The most potent agonist of human STING is 2’3’-cGAMP [2,3].
References:
1. Sun L. et al., 2013. Cyclic GMP-AMP synthase is a cytosolic DNA sensor that activates the type I interferon pathway. Science 339(6121):786-91.
2. Gao P. et al., 2013. Cyclic [G(2’,5’)pA(3’,5’)p] is the metazoan second messenger produced by DNA-activated cyclic GMP-AMP synthase. Cell. 153(5):1094-107.
3. Ablasser A. et al., 2013. cGAS produces a 2’-5’-linked cyclic dinucleotide second messenger that activates STING. Nature. 498(7454):380-4.
Chemical structure of TDI-6570
DOCUMENTS
Documents
Validation Data Sheet
Technical Data Sheet
Safety Data Sheet
Certificate of analysis
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