2. Immunology/Inflammation
  3. Cyclic GMP-AMP Synthase STING
  4. TDI-6570

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.

For research use only. We do not sell to patients.

TDI-6570

TDI-6570 Chemical Structure

CAS No. : 2287331-29-5

Size Price Stock Quantity
5 mg In-stock
10 mg In-stock
25 mg In-stock
50 mg In-stock
100 mg In-stock
200 mg   Get quote  
500 mg   Get quote  

* Please select Quantity before adding items.

This product is a controlled substance and not for sale in your territory.

Customer Review

Based on 1 publication(s) in Google Scholar

TDI-6570 Related Antibodies

Top Publications Citing Use of Products

  • Biological Activity

  • Purity & Documentation

  • References

  • Customer Review

Description

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[1][2][3].

In Vitro

TDI-6570 (TDI-006570) inhibited cGAMP production by human cGAS with an IC50 of 0.138 μM[1].
TDI-6570 (0.1-10 μM; single incubation for cGAS activity reaction) potently inhibits recombinant mouse cGAS activity in a cell-free system with an IC50 of 1.64 μM[2].
TDI-6570 (0.1-10 μM; single incubation concurrent with HT-DNA stimulation) potently inhibits cGAS-dependent IFN responses in BV2 mouse microglial reporter cells with an IC50 of 1.64 μM[2].
TDI-6570 specifically inhibits cGAS-dependent CXCL10 and CCL2 cytokine secretion in primary mouse microglia stimulated with HT-DNA[2].
TDI-6570 (100 μM; 24 h) is non-toxic to primary mouse neurons, microglia, and astrocytes at concentrations up to 100 μM after 24 h of incubation[2].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

TDI-6570 Related Antibodies

Cell Cytotoxicity Assay[2]

Cell Line: Primary mouse neurons, microglia, and astrocytes
Concentration: 0.3-100 μM
Incubation Time: 24 h
Result: Showed non-toxic to primary mouse neurons, microglia, and astrocytes at concentrations up to 100 μM.
In Vivo

TDI-6570 (150 mg/kg; oral; daily; 3 months) enhances the neuronal MEF2C transcriptional network, rescues synaptic integrity and plasticity, and restores cognitive function in a mouse model of tauopathy-associated Alzheimer's disease[2].
TDI-6570 (25-300 mg/kg; oral gavage; chow diet; single dose, 1 month, 3 months) inhibits cGAS-STING signaling in tauopathy mice, reduces tau spread by ~35%, recapitulates transcriptomic changes of the neuroprotective APOE3-R136S mutation in microglia and neurons, and reverses tau-induced synaptic loss when administered after disease onset[3].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: P301S mice (male, female, human MAPT transgene with P301S mutation; 3.5-4.5-month-old, tau seeding/spread model); E3/P301S mice (male, human APOE3 knockin crossed with P301S mice; 6-month-old, established tau pathology model)[3]
Dosage: 25 mg/kg (target engagement); 15 mg/kg (tau spread, weekday); 150 mg/kg (tau spread, weekend); 300 mg/kg diet (chronic post-onset)
Administration: oral gavage, single dose (target engagement); oral gavage, daily Monday-Friday for 1 month + chow diet, over weekends for 1 month (tau spread); chow diet, ad libitum for 3 months (chronic post-onset)
Result: Reduced STING protein levels and pTBK1/STING activation in frontal cortex at 6 hours post-treatment, and decreased STING-GM130 colocalization in IBA1+ microglia by ~35% relative to control.
Reduced MC-1-positive tau spread to the contralateral hippocampus by ~35% relative to control.
Induced 163 overlapping differentially expressed genes (DEGs) with the APOE3-R136S mutation in microglia (R=0.92), 609 overlapping DEGs in excitatory neurons (R=0.95), and 31 overlapping DEGs in inhibitory neurons (R=0.98); overlapping DEGs were enriched in pathways including cell motility, endocytosis, synaptic transmission, and cell morphogenesis.
Restored PSD95 immunofluorescence levels in E3/P301S mice to levels seen in APOE3-R136S/P301S mice, reversing tau-induced synaptic loss.
Animal Model: C57BL/6J P301S transgenic (male, 6-7-month-old, Alzheimer's disease tauopathy model); non-transgenic littermates (male, 6-7-month-old)[2]
Dosage: 150 mg/kg
Administration: oral; daily; 3 months
Result: Showed significant novel object recognition preference (P = 0.00167) in P301S transgenic mice.
Increased long-term potentiation magnitude in the hippocampal CA1 region of P301S mice by ~50% (P = 0.0058).
Rescued tauopathy-induced loss of excitatory (PSD-95, P = 0.043) and inhibitory (vGAT, P = 0.032) synapses in the hippocampal CA1 stratum radiatum of P301S mice.
Upregulated the MEF2C transcriptional network in both excitatory and inhibitory neuron clusters of P301S mice, with strong enrichment of MEF2C target genes (odds ratio = 13.4 for excitatory neurons, 9.8 for inhibitory neurons, -log(P overlap) > 10).
Molecular Weight

296.72

Formula

C14H14ClFN2O2
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

O=C(CO)N1CC2=C(CC1)N(C)C3=C2C=CC(Cl)=C3F
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 3.33 mg/mL (11.22 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 1 mg 5 mg 10 mg
1 mM 3.3702 mL 16.8509 mL 33.7018 mL
5 mM 0.6740 mL 3.3702 mL 6.7404 mL
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

  • Molarity Calculator

  • Dilution Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass
=
Concentration
×
Volume
×
Molecular Weight *

Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

Concentration (start)

C1

×
Volume (start)

V1

=
Concentration (final)

C2

×
Volume (final)

V2

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

Dosage

mg/kg

Animal weight
(per animal)

g

Dosing volume
(per animal)

μL

Number of animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Calculation results:
Working solution concentration: mg/mL
Purity & Documentation

Purity: 99.64%

SDS (251 KB)

COA (249 KB) HNMR (259 KB) LCMS (92 KB)

Handling Instructions (2659 KB)
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 3.3702 mL 16.8509 mL 33.7018 mL 84.2545 mL
5 mM 0.6740 mL 3.3702 mL 6.7404 mL 16.8509 mL
10 mM 0.3370 mL 1.6851 mL 3.3702 mL 8.4255 mL
  • No file chosen (Maximum size is: 1024 Kb)
  • If you have published this work, please enter the PubMed ID.
  • Your name will appear on the site.

TDI-6570 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

TDI-65702287331-29-5TDI-006570TDI6570TDI 6570TDI006570TDI 006570Cyclic GMP-AMP SynthaseSTINGcGASStimulator of Interferon GenesTMEM173MITAERISMPYSdouble-stranded DNAMEF2CBV2 mouse microglial reporter cellshippocampal CA1 long-term potentiationcGAS-STING-IFN signaling pathwayTBK1interferon-stimulated genecyclic GMP-AMP synthase (cGAS)tauInhibitorinhibitorinhibit

Your Recently Viewed Products:

Inquiry Online

Your information is safe with us. * Required Fields.

Product Name

  

Requested Quantity *

Applicant Name *

 

Salutation

Email Address *

 

Phone Number *

Department

 

Organization Name *

City

State

Country or Region *

      

Remarks

Bulk Inquiry

Inquiry Information

Product Name:
TDI-6570
Cat. No.:
HY-164288
Quantity:
MCE Japan Authorized Agent:

Customer Review

Thank You for Your Feedback!

Request for HNMR Report

Please fill out this form to request the QC report. We will send it to your Email address shortly.

Your information is safe with us. * Required Fields.

Product Name

  

Lot #

Applicant Name *

 

Email Address *

Phone Number

 

Department *

Organization Name *

 

Country or Region *

Remarks

SAFETY DATA SHEET (SDS)

English - EN (251 KB) Français - FR (251 KB) Deutsch - DE (251 KB) Norwegian - NO (251 KB) Español - ES (251 KB) Swedish - SV (251 KB) Italian - IT (251 KB) Korean - KR (251 KB) Portuguese - PT (251 KB)

Request for HNMR Report

We have received your request and will respond to you as soon as possible.