TDI-6570 - Mouse cGAS Inhibitor

InvitroFit™ PRR inhibitor

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].

More details More details

 

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.

 

Learn more Read our review on cGAS.

 

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.

Inhibition of cGAS signaling by TDI-6570
Inhibition of cGAS signaling by TDI-6570

InvitroFit™

InvitroFit™ is a high-quality standard specifically adapted for in vitro studies of inhibitors. InvitroFit™ products are 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

Synonyms
1-(7-chloro-6-fluoro-5-methyl-1,3,4,5-tetrahydro-2H-pyrido[4,3-b]indol-2-yl)-2-hydroxyethan-1-one
CAS number
2287331-29-5
Chemical formula

C14H14CIFN2O2

Molecular weight
296.7 g/mol
Purity
≥ 95% (UHPLC)
Solubility

5 mg/ml in DMSO. Product may require heating to 37°C for complete dissolution

Working concentration

0.01 - 1 µM (depending on the agonist; see VDS for more details)

Endotoxin

Negative (tested using EndotoxDetect™ assay)

Tested applications

In vitro cellular assays

Quality control

Each lot is functionally tested and validated using cellular assays.

CONTENTS

Contents

  • Product: 
    TDI-6570
  • Cat code: 
    inh-tdi6570-1
  • Quantity: 
    2 mg
Notes:

TDI-6570 is provided as a translucent film.

Shipping & Storage

  • Shipping method:  Room temperature

    • Storage:

    • -20°C
    Stability: Reconstituted product is stable for at least 6 months at -20 °C.

    Caution:

    • Avoid repeated freeze-thaw cycles

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

Chemical structure of TDI-6570

DOCUMENTS

Documents

TDI-6570

Technical Data Sheet

Validation Data Sheet

Safety Data Sheet

Certificate of analysis

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