For research use only.

Catalog No.S2714

17 publications

LY411575 Chemical Structure

CAS No. 209984-57-6

LY411575 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), also inhibits Notch cleavage with IC50 of 0.39 nM in APP or NΔE expressing HEK293 cells. LY411575 induces apoptosis.

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10mM (1mL in DMSO) USD 340 In stock
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Selleck's LY411575 has been cited by 17 publications

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  • (E) Quantitation of lumen from A-D. (F) RNA isolated from 6d acini and expression of NOTCH1 measured by qRT-PCR in triplicate. P values are * <.01, *** <0.001.

    Exp Cell Res, 2017, 359(2):384-393. LY411575 purchased from Selleck.

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Biological Activity

Description LY411575 is a potent γ-secretase inhibitor with IC50 of 0.078 nM/0.082 nM (membrane/cell-based), also inhibits Notch cleavage with IC50 of 0.39 nM in APP or NΔE expressing HEK293 cells. LY411575 induces apoptosis.
γ secretase (membrane-based) [1]
(HEK293 cells expressing either APP or NΔE)
γ secretase (cell-based) [1]
(HEK293 cells expressing either APP or NΔE)
Notch S3 cleavage [1]
(HEK293 cells expressing either APP or NΔE)
0.078 nM 0.082 nM 0.39 nM
In vitro

LY-411575 inhibits γ-secretase which can be assessed by the substrates like amyloid precursor protein (APP) and Notch S3 cleavage. [1] LY-411575, which blocks Notch activation, results in apoptosis in primary and immortalized KS cells. [2]

Cell Data
Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID
HEK293 cells MX\GeY5kfGmxbjDhd5NigQ>? NY\BR2xxUW6qaXLpeIlwdiCxZjDnZY1u[SC|ZXPy[ZRie2ViaX6gbJVu[W5iSFXLNlk{KGOnbHzzJIF{e2W|c3XkJIF{KGGveXzvbYQh[mW2YTC0NEBxem:mdXP0bY9vNCCHQ{WwQVAvODByMUG5JO69VQ>? NV\sb2JROTd3N{OzOFY>
CHO cells NWn5RVZkTnWwY4Tpc44h[XO|YYm= Mlq0NlQhcA>? MmDBVoVlfWO2aX;uJI9nKGi3bXHuJHBUOSCmZXz0ZUBmgG:wOTDteZRidnRvaX7keYNm\CCjbYnsc4llKGKndHGtOFIhdGW4ZXygbY4hS0iRIHPlcIx{KG:4ZYLlfJBz\XO|aX7nJIh2dWGwIFHQVFc2OWGodHXyJFI1KGi{czDifUBtcXG3aXSgdIhie2ViZXzlZ5Rzd2OqZX3pcJVucW6nc3PlcoNmKGG|c3H5JJJmdGG2aY\lJJRwKGOxboTyc4wtKEWFNUC9NE4xODB|NUKg{txO NXXSXHd1OTd3N{OzOFY>
CHO cells M33EZ2Z2dmO2aX;uJIF{e2G7 NEXRdIszPCCq M4[3enJm\HWldHnvckBw\iCqdX3hckBRWzFiZHXseIEh\XixbkmgcZV1[W62LXnu[JVk\WRiYX35cI9q\CCkZYThMVQxKGyndnXsJIlvKEOKTzDj[YxteyCxdnXy[ZhxemW|c3nu[{BpfW2jbjDBVHA4PTGjZoTldkAzPCCqcoOgZpkhdGmzdXnkJJBp[XOnIHXs[YN1em:laHXtbYx2dWmwZYPj[Y5k\SCjc4PhfUBz\WyjdHn2[UB1dyClb370do9t M4K4XFE4PTd|M{S2
CHO cells NED2TWRHfW6ldHnvckBie3OjeR?= MYKyOEBp MWXS[YR2[3Srb36gc4YhcHWvYX6ge4lt\CC2eYDlJHBUOS2rbnT1Z4VlKGGveXzvbYQh[mW2YT20NEBt\X[nbDDpckBEUE9iY3XscJMhd3[ncnX4dJJme3OrbnegbJVu[W5iQWDQO|UyKGGodHXyJFI1KGi{czDifUBtcXG3aXSgdIhie2ViZXzlZ5Rzd2OqZX3pcJVucW6nc3PlcoNmKGG|c3H5JJJmdGG2aY\lJJRwKGOxboTyc4wtKEWFNUC9NE4xODBzMUSg{txO NXTHXGZmOTd3N{OzOFY>
CHO cells NF3wZodHfW6ldHnvckBie3OjeR?= MYOyOEBp NWrKSGFTWmWmdXP0bY9vKG:oIHj1cYFvKHerbHSgeJlx\SCSU{GtbY5lfWOnZDDhcZltd2mmIHLleIEuPDJibHX2[YwhcW5iQ1jPJINmdGy|IH;2[ZJmgHC{ZYPzbY5oKGi3bXHuJGFRWDd3MTDh[pRmeiB{NDDodpMh[nlibHnxeYllKHCqYYPlJIVt\WO2cn;jbIVucWy3bXnu[ZNk\W6lZTDhd5NigSC{ZXzheIl3\SC2bzDjc451em:uLDDFR|UxRTBwMECwNVM2KM7:TR?= NXjzZod5OTd3N{OzOFY>
H4 cells M2HGPWZ2dmO2aX;uJIF{e2G7 NEjOfW4yODBibl2= NYfCSnJjOTZiaB?= Mlf3TY5pcWKrdHnvckBw\iCpYX3tZUB{\WO{ZYThd4Uh\XiycnXzd4VlKGmwIHj1cYFvKEh2IHPlcIx{KGW6cILld5NqdmdiQmLJMWM6QSCodYPpc44heHKxdHXpckBie3Onc4Pl[EBieyCFOUmg[pJi\22nboSgZYNkfW23bHH0bY9vKG[{YXft[Y51KGG2IEGwNEBvVSCrbnP1ZoF1\WRiZn;yJFE3KGi{czDpckBjgSCrbX31co9jdG:2 NH7OOWozOzF6MUWwNi=>
H4 cells M3fSOGZ2dmO2aX;uJIF{e2G7 M2nsNlExOCCwTR?= MlXQNVYhcA>? MYDJcohq[mm2aX;uJI9nKGejbX3hJJNm[3KndHHz[UBmgHC{ZYPz[YQhcW5iaIXtZY4hUDRiY3XscJMh[XO|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJGM5OyCuZY\lcJMh[XRiMUCgeW0hcW6ldXLheIVlKG[xcjCxOkBpenNiYomgbY1ufW6xYnzveC=> MX2yN|E5OTVyMh?=
H4 cells M3HJWGZ2dmO2aX;uJIF{e2G7 NFPQN4wyOCC3TR?= MkD4NVYhcA>? MYfJcohq[mm2aX;uJI9nKGejbX3hJJNm[3KndHHz[UBmgHC{ZYPz[YQhcW5iaIXtZY4hUDRiY3XscJMh[XO|ZYPz[YQh[XNicnXkeYN1cW:wIHnuJGNVTiCuZY\lcJMh[XRiMUCgeW0hcW6ldXLheIVlKG[xcjCxOkBpenNiYomgbY1ufW6xYnzveC=> MmW2NlMyQDF3MEK=
HEK293 cells NH\HNYtHfW6ldHnvckBie3OjeR?= MkDPN{Bl[Xm| NITQd|ROd2S3bHH0bY9vKG:oIHfhcY1iNXOnY4LleIF{\SCrbjDISWszQTNiY3XscJMh\XiycnXzd4lv\yCpdXnu[YEheGmpIGP3[YRqe2hibYX0ZY51KFOIVj3BVHA3QTW|dzDjc4V5eHKnc4PpcochTEyONDDhd5Nme3OnZDDhd{BqdmirYnn0bY9vKG:oIH7veINpKHC{b3Pld5NqdmdiaX6gbJVu[W5iVFW2O|Eh[2WubIOgZYZ1\XJiMzDkZZl{KGK7IHT1ZYwu[2WubDDseYNq\mW{YYPlJJJmeG:{dHXyJIdmdmViYYPzZZktKEmFNUC9NU4zKM7:TR?= MVqyOFE{QTV6Mx?=

... Click to View More Cell Line Experimental Data

In vivo 10 mg/kg oral dose of LY-411575 decreases brain and plasma Aβ40 and -42 dose-dependently. [1] LY-411575 reduces cortical Aβ40 in young (preplaque) transgenic CRND8 mice (ED50 ≈ 0.6 mg/kg) and produces significant thymus atrophy and intestinal goblet cell hyperplasia at higher doses (>3 mg/kg). The therapeutic window is similar after oral and subcutaneous administration and in young and aged CRND8 mice. Both the thymus and intestinal side effects are reversible after a 2-week washout period. Three-week treatment with 1 mg/kg LY411575 reduces cortical Aβ40 by 69% without inducing intestinal effects, although a previously unreported change in coat color is observed. [3]


Kinase Assay:


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Assays for Aβ and NICD:

Procedures for measuring γ-secretase activity in membranes prepared from HEK293 cells expressing APP have been described previously (Zhang L et al Biochemistry 40, 5049-5055). Intact HEK293 cells expressing either APP or NΔE are treated with various concentrations of LY- 411,575 for 4 hours at 37 °C. In the case of cells expressing NΔE, cells are lysed, the cell lysates are separated on a 4-12% NuPAGE gel, and the processed NICD fragment is detected via Western blot with a cleavage site-specific antibody. The inhibition of NICD production is quantified by spot densitometric analysis using FluorChem. In the case of cells expressing APP, the conditioned medium is collected, centrifuged at 10,000 × g for 5 minutes to remove cell debris, and stored at -20 °C prior to the determination of Aβ levels. Aβ40 and -42 produced in HEK293 membrane- and cell-based assays, as well as plasma Aβ40 and cortex Aβ40 from TgCRND8 mice, are analyzed without pretreatment using an electrochemiluminescence detection-based immunoassay. Plasma Aβ42 is measured by enzyme-linked immunosorbent assay. A commercially available enzyme-linked immunosorbent assay kit is used to measure cortex Aβ42 according to the manufacturer''s instructions.
Cell Research:


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  • Cell lines: primary and immortalized KS cells
  • Concentrations: 500 μM
  • Incubation Time: 24 hours
  • Method:

    DNA/PI staining is performed using standard methodologies. Briefly, 1 × 106 cells are permeabilized with 100% ethanol in the presence of 15% FBS. The cells are washed and then treated for 15 minutes at 37 °C with 10 mg/mL RNAse. PI (5 mg/mL) is added, and the cells incubated for 1 hour at 4 °C prior to analysis by flow cytometry with 10 000 cells analysed per gated determination. The results are confirmed using the Immunotech Annexin V staining kit following the manufacturers’ instructions. At least three independent experiments are performed showing similar results.(Only for Reference)

Animal Research:


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  • Animal Models: TgCRND8 mice model
  • Dosages: 1-10 mg/kg
  • Administration: Orally
    (Only for Reference)

Solubility (25°C)

In vitro DMSO 95 mg/mL (198.13 mM)
Ethanol 13 mg/mL (27.11 mM)
Water Insoluble
In vivo Add solvents to the product individually and in order(Data is from Selleck tests instead of citations):
30% PEG400+0.5% Tween80+5% propylene glycol
For best results, use promptly after mixing.
30 mg/mL

* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.

Chemical Information

Molecular Weight 479.48


CAS No. 209984-57-6
Storage powder
in solvent
Synonyms N/A
Smiles CC(C(=O)NC1C2=CC=CC=C2C3=CC=CC=C3N(C1=O)C)NC(=O)C(C4=CC(=CC(=C4)F)F)O

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Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

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Frequently Asked Questions

  • Question 1:

    Does this inhibitor act on beta-secretase?.

  • Answer:

    LY411575 has been reported to inhibit gamma-secretase, currently, there is no publication reporting its inhibition on beta-secreatse.

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Cell Lines Assay Type Concentration Incubation Time Formulation Activity Description PMID