A pan γ-secretase inhibitor
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Semagacestat

Item No. 16713

Product Insert (PDF)Safety Data Sheet (SDS) (PDF)
Technical Information
Formal Name
(2S)-2-hydroxy-3-methyl-N-[(1S)-1-methyl-2-oxo-2-[[(1S)-2,3,4,5-tetrahydro-3-methyl-2-oxo-1H-3-benzazepin-1-yl]amino]ethyl]-butanamide
CAS Number
425386-60-3
Synonyms
  • LY450139
Molecular Formula
C19H27N3O4
Formula Weight
361.4
Purity
≥95%
Formulation
A crystalline solid
Solubility(Learn about Variance in Solubility)
DMF: 25 mg/mlDMSO: 25 mg/mlEthanol: 1 mg/ml
SMILES
O=C1N(CCC(C=CC=C2)=C2[C@@H]1NC([C@H](C)NC([C@@H](O)C(C)C)=O)=O)C
InChi Code
InChI=1S/C19H27N3O4/c1-11(2)16(23)18(25)20-12(3)17(24)21-15-14-8-6-5-7-13(14)9-10-22(4)19(15)26/h5-8,11-12,15-16,23H,9-10H2,1-4H3,(H,20,25)(H,21,24)/t12-,15-,16-/m0/s1
InChi Key
PKXWXXPNHIWQHW-RCBQFDQVSA-N
Shipping & Storage Information
Storage
-20°C
Shipping
Room temperature in continental US; may vary elsewhere
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    1 mg

    $41

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    5 mg

    $99

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    10 mg

    $178

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    25 mg

    $389

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    Product Description

    Semagacestat is a potent inhibitor of γ-secretase that blocks the production of Aβ38, Aβ40, and Aβ42 with IC50 values of 12.0, 12.1, and 10.9 nM, respectively.1,2 It also blocks Notch signaling (IC50 = 14.1 nM).2 Semagacestat modulates γ-secretase activity in vivo, altering Aβ levels in brain, cerebrospinal fluids, and plasma in a dose-dependent fashion.1,2 Although semagacestat does not improve cognitive status in humans, it is useful as a pan γ-secretase inhibitor for research purposes.2,3

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. Lanz, T.A., Karmilowicz, M.J., Wood, K.M., et al. Concentration-dependent modulation of amyloid-β in vivo and in vitro using the γ-secretase inhibitor, LY-450139. J. Pharmacol. Exp. Ther. 319(2), 924-933 (2006).

    2. Mitani, Y., Yarimizu, J., Saita, K., et al. Differential effects between γ-secretase inhibitors and modulators on cognitive function in amyloid precursor protein-transgenic and nontransgenic mice. J. Neurosci. 32(6), 2037-2050 (2012).

    3. Doody, R.S., Raman, R., Farlow, M., et al. A phase 3 trial of semagacestat for treatment of Alzheimer’s disease. N. Engl. J. Med. 369(4), 341-350 (2013).