SJ-300
SJ-300 is a potent and selective, orally active and brain-penetrat DKK3-LRP1 interaction inhibitor. SJ-300 restores Aβ clearance in AD models. SJ 300 binds to mLRPIV with a Kd of 7.9 μM, inhibits the DKK3 mLRPIV complex with an IC50 of 3.2 μM, and does not disrupt the binding of Aβ to LRP1. SJ 300 rescues cognitive function and ameliorates neuropathology (Aβ plaque reduction ≈ 73.3 %) in vivo. SJ 300 can be employed for research in Alzheimer’s disease.
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- CAS No.: 1210357-06-4
- Formule: C20H27FN4
- Masse moléculaire:342.45
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Help & FAQs
Activité biologique
Description
In Vitro
SJ-300 (0-5 μM) exerts a substantial reduction in the DKK3-mLRPIV interaction in SH-SY5Y cells[1].
SJ-300 (1 μM, 2 h) restores Aβ internalization in AD-NSC cells[1].
SJ-300 (10 μM) has no direct impact on the canonical Wnt/β-catenin signaling pathway in SH-SY5Y cell. [1].
SJ-300 (50 μM in 2 μL0-60 min) has superior metabolic stability in mouse and human liver microsomes[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Cell Line:AD-NSC cell
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Concentration:1 μM
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Incubation Time:2 h
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Result:Restored Aβ internalization in cells treated with DKK3 but in treated with DKK1.
Parmacokinetics
| Species | Dose | Route | T1/2 | Tmax | Cmax | AUC0-24 | AUC0-inf | Vz-F_obs | MRT | F | ClF_obs |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Mice | 10 mg/kg | i.g. | 11.2 h | 1 h | 178 ng/mL | 1721 ng·h/mL | 2280 ng·h/mL | 72973 mL/h/kg | 7.7965 h | 71.30 % | / |
| Mice | 2 mg/kg | i.v. | 11.2 h | 0.079 h | 74.2 ng/mL | 483 ng·h/mL | 538 ng·h/mL | 52931 mL/kg | 7.2043 h | / | 3732 mL/h/kg |
In Vivo
SJ-300 (i.g., 10 mg/kg, once) shows a brain-penetration capability with brain/plasma (B/P) ratio = 5732 %[1].
SJ-300 (i.g., 5 mg/kg, once daily for 8 weeks) improves cognitive functions in the 5×FAD transgenic mouse (6 months) model of AD, and these improvements associate with reductions in Aβ pathology.[1].
SJ-300 (i.g., 5 mg/kg, once daily for 8 weeks) attenuates cognitive deficits and AD pathologies through enhancing Aβ clearance in 6-month-old 5×FAD mice.[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:5×FAD transgenic mouse model of AD (16 weeks)[1]
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Dosage:5 mg/kg
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Administration:i.g., once daily for 8 weeks
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Result:Reduced escape latencies during the 5-day acquisition phase.
Increased time spent in the target quadrant, and number of platform crossings during the probe trials.
Enhanced spatial working memory in the Y-maze test.
Reduced the number of Aβ plaques of various diameters in both brain regions.
Decreased the total number of Aβ plaques by approximately 73.3%.
Decreased the clustering of astrocytes by 64.1 % and microglia around the plaques.
Reduced both soluble and insoluble Aβ levels.
Did not affect APP cleavage or Aβ production.
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Animal Model:5×FAD transgenic mouse model of AD (6 months)[1]
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Dosage:5 mg/kg
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Administration:i.g., once daily for 8 weeks
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Result:Did not alter LRP1 expression but reduced colocalized Aβ on brain vascular basement membranes and endothelium.
Reduced the levels of both Aβ40 and Aβ42 in the plasma and liver of treated mice.
Did not alter the circulating concentrations of soluble LRP1.
Inhibited the association between soluble LRP1 (sLRP1) and DKK3.
Chemical Information
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CAS No. 1210357-06-4
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Masse moléculaire 342.45
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Formule C20H27FN4
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SMILES
FC1=CC=C(N2N=C(C)C(CNC3CCN(C4CC4)CC3)=C2C)C=C1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
SJ-300 Related Classifications
HY-179459 Related Classifications
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