A γ-secretase inhibitor
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LY411575

Item No. 16162

Product Insert (PDF)Safety Data Sheet (SDS) (PDF)
Technical Information
Formal Name
N-[(1S)-2-[[(7S)-6,7-dihydro-5-methyl-6-oxo-5H-dibenz[b,d]azepin-7-yl]amino]-1-methyl-2-oxoethyl]-3,5-difluoro-αS-hydroxy-benzeneacetamide
CAS Number
209984-57-6
Molecular Formula
C26H23F2N3O4
Formula Weight
479.5
Purity
≥98%
Formulation (Request formulation change)
A crystalline solid
Solubility(Learn about Variance in Solubility)
DMSO: Slightly soluble: 0.1-1 mg/mlMethanol: Slightly soluble: 0.1-1 mg/ml
λmax
233 nm
SMILES
FC1=CC([C@H](O)C(N[C@@H](C)C(N[C@H]2C(C=CC=C3)=C3C(C=CC=C4)=C4N(C)C2=O)=O)=O)=CC(F)=C1
InChi Code
InChI=1S/C26H23F2N3O4/c1-14(29-25(34)23(32)15-11-16(27)13-17(28)12-15)24(33)30-22-20-9-4-3-7-18(20)19-8-5-6-10-21(19)31(2)26(22)35/h3-14,22-23,32H,1-2H3,(H,29,34)(H,30,33)/t14-,22-,23-/m0/s1
InChi Key
ULSSJYNJIZWPSB-CVRXJBIPSA-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

    $128

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    10 mg

    $235

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    25 mg

    $487

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    Product Description

    γ-Secretase is a multi-subunit aspartyl protease that regulates signaling pathways by proteolytically cleaving substrates, abrogating or releasing signaling molecules. One well-known substrate of this enzyme is Notch, a transmembrane receptor that plays a key role in cell fate decisions including cell proliferation, differentiation, and apoptosis. LY411575 is a cell-permeable γ-secretase inhibitor (IC50 = 0.14 nM) that has been shown to block Notch activation in vitro at 500 µM.1,2 LY411575 can induce apoptosis in Kaposi’s sarcoma cells as well as promote intestinal goblet cell differentiation in a mouse model of colitis.2,3 It has also been observed to promote neural differentiation of mouse embryonic stem cells.4

    WARNING This product is not for human or veterinary use.

    References & Product Citations
    Product Description References

    1. Czirr, E., Leuchtenberger, S., Dorner-Ciossek, C., et al. Insensitivity to Aβ42-lowering nonsteroidal anti-inflammatory drugs and γ-secretase inhibitors is common among aggressive presenilin-1 mutations. The Journal of Biological Chemisty 282(34), 24504-24513 (2007).

    2. Curry, C.L., Reed, L.L., Golde, T.E., et al. Gamma secretase inhibitor blocks Notch activation and induces apoptosis in Kaposi’s sarcoma tumor cells. Oncogene 24(42), 6333-6344 (2005).

    3. Okamoto, R., Tsuchiya, K., Nemoto, Y., et al. Requirement of Notch activation during regeneration of the intestinal epithelia. Am. J. Physiol. Gastrointest. Liver Physiol. 296(1), G23-G35 (2009).

    4. Abranches, E., Silva, M., Pradier, L., et al. Neural differentiation of embryonic stem cells in vitro: A road map to neurogenesis in the embryo. PLoS One 4(7), e6286 (2009).