EVP-0015962
EVP-0015962 is an orally active, blood-brain barrier-permeable γ-secretase inhibitor with an IC50 of 3.9 μM. EVP-0015962 alters γ-secretase-mediated cleavage of amyloid precursor protein, reduces Aβ42 production and increases Aβ38 production. EVP-0015962 reduces Aβ aggregates, amyloid plaques and inflammatory markers in the brains of mice, and improves their cognitive impairment. EVP-0015962 can be used for the research of Alzheimer's disease.
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- No. CAS: 1447811-26-8
- Fòrmula: C22H19ClF6O3
- Peso molecular:480.83
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Almacenamiento:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Actividad biológica
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Cell Line
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Type | Value | Description | References |
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| H4 | IC50 |
67 nM
Compound: EVP-0015962
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Modulation of gamma-secretase in human H4 cells expressing wild type APP751 assessed as inhibition of intracellular amyloid beta 42 production after 16 to 18 hrs by sandwich ELISA
Modulation of gamma-secretase in human H4 cells expressing wild type APP751 assessed as inhibition of intracellular amyloid beta 42 production after 16 to 18 hrs by sandwich ELISA
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[PMID: 26142947] |
EVP-0015962 (0.003-10 μM; 16-18 h) acts as a γ-secretase modulator in H4-APP751 cells, potently decreasing Aβ42 (IC50 = 67 nM) and increasing Aβ38 without altering total Aβ levels at non-cytotoxic concentrations[1].
EVP-0015962 (0.01-30 μM; 24 h) modulates γ-secretase in rat primary neocortical cultures, decreasing Aβ42 (IC50 = 427 nM) and increasing Aβ38 without reducing Aβ1-ₓ levels or inducing cytotoxicity at active concentrations[1].
EVP-0015962 (0.001-100 μM; 3 h) modulates γ-secretase in a cell-free reconstituted system, selectively lowering Aβ42 (IC50 = 3.9 μM) without inhibiting AICD production or altering Aβ40 levels[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
EVP-0015962 (20-60 mg/kg/day; p.o.; continuous via food formulation; 50 weeks) is well-tolerated in male Tg2576 mice, reduces brain Aβ42 levels by 53-89%, aggregated Aβ by 73% at the high dose, amyloid plaque burden, and reactive gliosis, with a dose-dependent trend in efficacy[1].
EVP-0015962 (20-60 mg/kg/day; p.o.; continuous via food formulation; 11 weeks) reverses the contextual fear conditioning cognitive deficit in 30-33-week-old male Tg2576 mice[1].
EVP-0015962 (30 mg/kg; p.o.; single dose) does not reverse the contextual fear conditioning cognitive deficit in 30-week-old male Tg2576 mice[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:Tg2576 (B6;SJL-Tg(APPSWE)2576Kha) (male, 21 weeks old, 24-35 g)[1]
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Dosage:10 mg/kg; 30 mg/kg
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Administration:p.o.; single dose
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Result:Reduced brain Aβ42 levels by 22% relative to vehicle controls (not statistically significant).
Reduced brain Aβ42 levels by 39% relative to vehicle controls.
Left AβTotal levels unchanged with both doses.
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Animal Model:Tg2576 (B6;SJL-Tg(APPSWE)2576Kha) (male, 17-26 weeks old at study start)[1]
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Dosage:20 mg/kg/day; 60 mg/kg/day
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Administration:p.o.; continuous via food formulation; 50 weeks
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Result:Achieved brain concentrations of 2.5 μM (20 mg/kg/day group) and 8.3 μM.
Reduced TBS-soluble Aβ42 by 53% in the 20 mg/kg/day group and 89% in the 60 mg/kg/day group relative to controls.
Reduced formic acid-extractable Aβ42 by 53% in the 20 mg/kg/day group and 86% in the 60 mg/kg group relative to controls.
Increased TBS-soluble Aβ38 by 78% in the 60 mg/kg/day group relative to controls; the 20 mg/kg/day group showed no significant increase.
Reduced formic acid-extractable AβTotal by 49% in the 20 mg/kg/day group and 64% in the 60 mg/kg/day group relative to controls.
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Animal Model:Tg2576 (B6;SJL-Tg(APPSWE)2576Kha) (male, 19-22 weeks old at study start, tested at 30-33 weeks old)[1]
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Dosage:20 mg/kg/day; 60 mg/kg/day
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Administration:p.o.; continuous via food formulation; 11 weeks
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Result:Reversed the cognitive deficit (reduced percent freezing) in Tg2576 mice completely, with percent freezing levels in both treatment groups not significantly different from wild-type controls and significantly higher than control diet Tg2576 mice.
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Animal Model:Tg2576 (B6;SJL-Tg(APPSWE)2576Kha) (male, 30 weeks old)[1]
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Dosage:30 mg/kg
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Administration:p.o.; single dose
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Result:Did not reverse the genotype-associated cognitive deficit (reduced percent freezing) in Tg2576 mice relative to wild-type mice; percent freezing levels in EVP-0015962-treated Tg2576 mice remained significantly lower than those in EVP-0015962-treated wild-type mice.
Chemical Information
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No. CAS 1447811-26-8
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Peso molecular 480.83
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Fòrmula C22H19ClF6O3
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SMILES
O=C([C@@H](C1=CC(C2=CC=C(C=C2)C(F)(F)F)=C(C(Cl)=C1)OCC(F)(F)F)CC3CCC3)O
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Envío
Room temperature in continental US; may vary elsewhere.
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Almacenamiento
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureza y Documentación
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Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
EVP-0015962 Related Classifications
HY-117521 Related Classifications
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