TDI-6570
Based on 1 Customer Validation
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.
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- Purity: 99.64%
- CAS No.: 2287331-29-5
- 화학식: C14H14ClFN2O2
- 분자량:296.72
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보관:Powder -20°C, 3 years ; In solvent -80°C, 6 months , -20°C, 1 month
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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용액&용해도
- 순도&문서
- References
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Help & FAQs
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Biological Activity
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.
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Cell Line:Primary mouse neurons, microglia, and astrocytes
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Concentration:0.3-100 μM
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Incubation Time:24 h
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Result:Showed non-toxic to primary mouse neurons, microglia, and astrocytes at concentrations up to 100 μM.
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.
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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]
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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)
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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)
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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.
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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]
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Dosage:150 mg/kg
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Administration:oral; daily; 3 months
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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).
Chemical Information
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CAS No. 2287331-29-5
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Appearance Solid
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분자량 296.72
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화학식 C14H14ClFN2O2
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Color White to off-white
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SMILES
O=C(CO)N1CC2=C(CC1)N(C)C3=C2C=CC(Cl)=C3F
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Synonyms
TDI-006570
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Powder -20°C 3 years In solvent -80°C 6 months -20°C 1 month
용액&용해도
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)
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.
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.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
순도&문서
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Data Sheet (280 KB)
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SDS (251 KB)
- 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)
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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 |
TDI-6570 Related Classifications
HY-164288 Related Classifications
Powered by Bioz
- TDI-6570
- 2287331-29-5
- TDI-006570
- TDI6570
- TDI 6570
- TDI006570
- TDI 006570
- Cyclic GMP-AMP Synthase
- STING
- double-stranded DNA
- MEF2C
- BV2 mouse microglial reporter cells
- hippocampal CA1 long-term potentiation
- cGAS-STING-IFN signaling pathway
- TBK1
- interferon-stimulated gene
- cyclic GMP-AMP synthase (cGAS)
- tau
- Inhibitor
- inhibitor
- inhibit