FTO-IN-17
FTO-IN-17 is an orally active and brain-penetrant FTO (m6A RNA demethylase) inhibitor with an IC50 of 1.1 μM. FTO-IN-17 stably binds the FTO catalytic pocket. FTO-IN-17 protects against Aβ1-42-induced toxicity while increasing global m6A levels and dampening pro-inflammatory gene (CXCL10, TNF-α) expression. FTO-IN-17 ameliorates anxiety-like behavior and rescues hippocampal-dependent spatial, recognition memory and neuroinflammation in Alzheimer's disease mice models.
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- CAS No.: 1434867-98-7
- Formula: C20H23FN4O2
- Molecular Weight:370.42
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Help & FAQs
Biological Activity
FTO-IN-17 (Compound VI) exhibits high in vitro blood-brain barrier permeability (Pe = 12.2 × 10-6 cm/s)[1].
FTO-IN-17 (0.01-50 μM; overnight) potently inhibits human FTO demethylase activity with an IC50 of 1.1 μM[1].
FTO-IN-17 (10 μM; overnight) is fully selective for human FTO over human ALKBH5 demethylase, showing no inhibition of ALKBH5 at 10 μM[1].
The (S)-stereoisomer of FTO-IN-17 exhibits significantly stronger, more stable binding to human FTO than the (R)-stereoisomer, with over 7 times higher calculated binding affinity[1].
FTO-IN-17 (0.001-50 μM; 30 min pre-incubation + 24 h co-incubation) provides sustained, dose-dependent neuroprotection against Aβ1-42-induced toxicity in differentiated SH-SY5Y cells, increases global m6A levels, and downregulates pro-inflammatory gene expression at 1 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:differentiated SH-SY5Y human neuroblastoma cells
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Concentration:0.001, 0.01, 0.1, 1, 10, 50 μM
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Incubation Time:30 min pre-incubation, followed by 24 h co-incubation with 5 μM Aβ1-42
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Result:Demonstrated dose-dependent neuroprotection, with 70-85% cell viability at 0.1-10 μM.
Significantly increased global m6A RNA methylation levels compared to Aβ1-42-treated cells at 1 μM.
Significantly downregulated mRNA expression of pro-inflammatory genes CXCL10, TNF-α, and HMOX1 at 1 μM.
| Species | Dose | Route | Cmax | Tmax | Cmax (Brain) | Tmax (Brain) | Brain-Kp |
|---|---|---|---|---|---|---|---|
| Mice[1] | 3 mg/kg | p.o. | 51.3 ng/mL | 5 min | 29.9 ng/g | 5 min | 58 % |
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Alzheimer's disease model (SAMP8, 5-month-old female; sporadic Alzheimer's disease model)[1]
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Dosage:3 mg/kg
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Administration:p.o.; daily; 28 days
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Result:Significantly reduced anxiety-like behavior via decreased rearing and grooming in the open field test.
Rescued hippocampal-dependent spatial memory, with object location test discrimination index recovered to levels comparable to SAMR1 control mice.
Significantly increased both short-term and long-term recognition memory relative to SAMP8 control mice via novel object recognition test discrimination indices.
Increased global m6A methylation levels in brain tissue.
Upregulated expression of synaptic plasticity genes Arc and Egr1 in brain tissue.
Downregulated expression of neuroinflammatory genes Cxcl10, iNOS, and Hmox1 in brain tissue.
Chemical Information
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CAS No. 1434867-98-7
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Molecular Weight 370.42
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Formula C20H23FN4O2
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SMILES
CC(C1=NOC(C2CCCN(C2)CC3=NC4=C(C=CC=C4C(O)=C3)F)=N1)C
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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