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Chemical Structure| 209984-57-6 Chemical Structure| 209984-57-6

Structure of LY-411575
CAS No.: 209984-57-6

Chemical Structure| 209984-57-6

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LY-411575 is a potent γ-secretase inhibitor with IC50 values of 0.078 nM and 0.082 nM (membrane/cell-based), and it also inhibits Notch S3 cleavage with an IC50 of 0.39 nM.

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Product Details of LY-411575

CAS No. :209984-57-6
Formula : C26H23F2N3O4
M.W : 479.48
SMILES Code : C[C@H](NC([C@H](C1=CC(F)=CC(F)=C1)O)=O)C(N[C@H]2C3=CC=CC=C3C4=CC=CC=C4N(C)C2=O)=O
MDL No. :MFCD09832551
InChI Key :ULSSJYNJIZWPSB-CVRXJBIPSA-N
Pubchem ID :10435235

Safety of LY-411575

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302
Precautionary Statements:P280-P305+P351+P338

Isoform Comparison

Biological Activity

In Vitro:

Cell Line
Concentration Treated Time Description References
μM1S cells 2 nM 4 hours significantly increased mBCMA molecules, reduced sBCMA levels PMC9381512
H929 cells 2 nM 1 day enhanced mBCMA molecules, mCD138 levels unchanged PMC9381512
KMS11 cells 2 nM 42 hours continuously increased mBCMA expression, sBCMA levels remained minimal PMC9381512
H929-KD cells 2 nM 1 day Significantly increased mBCMA density PMC9381512
U266-KD cells 2 nM 1 day Significantly increased mBCMA density PMC9381512
taste organoids 10 µM LY-411575 restored taste receptor cell generation in cisplatin-treated taste organoids, reduced the number of apoptotic cells, and increased the number of proliferative cells. PMC10240818
murine olfactory epithelium cells 5 μM 7 days promote the generation of mature olfactory sensory neurons in murine olfactory epithelium cells PMC7738855

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Mice APPswe/PS1dE9xYFP mice Oral gavage 0.01, 0.1 or 0.2 mM/l Administered at the onset of mechanical ventilation, lasted for 2 hours To evaluate the effects of LY-411575 on existing amyloid plaques and neuritic abnormalities. Results showed that LY-411575 significantly reduced Aβ levels in plasma and brain but had no significant effect on the size of existing plaques or plaque-associated neuritic abnormalities. PMC2687427
Mice Alzheimer's disease transgenic mouse model Oral 5 mg/kg Daily for 3 weeks LY-411575 significantly reduced soluble Aβ levels in the hippocampus of transgenic mice and restored normal neuronal activity, suggesting a causal relationship between soluble Aβ and neuronal hyperactivity. PMC3365221
NSG mice KMS11-luc multiple myeloma model oral gavage 10 mg/kg Single dose, observed 4-6 hours after treatment significantly enhanced the anti-MM efficacy of PL33 and prolonged host survival PMC9381512
Mice RML prion-infected model Oral 5 mg/kg bodyweight/day Once daily for 4 weeks The combination of GSI and Qa reduced PrPSc levels in the cortex and hippocampus and prevented dendritic atrophy and loss, but GSI alone failed to prevent dendritic degeneration. PMC2492499
CD1 mice RML prion infection model Oral 50 mg/kg Once daily for seven consecutive days LY-411575 alone significantly reduced NICD but did not prevent dendritic degeneration; combined with quinacrine (Qa), it significantly reduced PrPSc accumulation and prevented dendritic degeneration. PMC2825502
Mice APPswe/PS1dE9xYFP mice Oral gavage 5 mg/kg/day Once daily for 43 to 55 days To study the effects of LY-411575 on existing amyloid plaques and neuritic abnormalities. Results showed that LY-411575 significantly reduced Aβ levels in plasma and brain but had no significant effect on the size of existing plaques or neuritic abnormalities. PMC2687427
NSG mice KMS11-luc MM cell model Oral 0.1 mg/mL Once daily for 8, 15, or 26 days Significantly enhanced the anti-MM efficacy of PL33 and prolonged host survival PMC9381512
mice intraperitoneal injection 200 mg/kg Once daily for 7 consecutive days LY-411575 reduced the number of apoptotic cells and increased the number of proliferative cells induced by cisplatin in the circumvallate papilla. PMC10240818

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

2.09mL

0.42mL

0.21mL

10.43mL

2.09mL

1.04mL

20.86mL

4.17mL

2.09mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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