GSI-136
GSI-136 is an inhibitor of γ-secretase with an IC50 of 3 nM. GSI-136 can lead to a dose-dependent reduction of Aβ40 levels in diethylamine-extracted brain homogenates of C57BL/6 mice. GSI-136 can be studied in medicinal chemistry and Alzheimer's disease research.
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- CAS No.: 443989-01-3
- 화학식: C11H18ClNO3S2
- 분자량:311.85
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보관:
Please store the product under the recommended conditions in the Certificate of Analysis.
Biological Activity
제품 설명
Cellular Effect
|
Cell Line
|
Type | Value | Description | References |
|---|---|---|---|---|
| CHO | EC50 |
29 nM
Compound: 1
|
Inhibition of gamma-secretase-mediated cleavage of human APP expressed in CHO cells assessed as reduction in amyloid beta40 production after 24 hrs by double sandwich ELISA
Inhibition of gamma-secretase-mediated cleavage of human APP expressed in CHO cells assessed as reduction in amyloid beta40 production after 24 hrs by double sandwich ELISA
|
[PMID: 19443228] |
| CHO | EC50 |
29 nM
Compound: 1
|
Inhibition of gamma-secretase-mediated cleavage of human APP expressed in CHO cells assessed as reduction in amyloid beta42 production after 24 hrs by double sandwich ELISA
Inhibition of gamma-secretase-mediated cleavage of human APP expressed in CHO cells assessed as reduction in amyloid beta42 production after 24 hrs by double sandwich ELISA
|
[PMID: 19443228] |
| CHO | IC50 |
25 nM
Compound: 9
|
Inhibition of gamma-secretase expressed in CHO cells expressing human recombinant APP assessed as amyloid beta40 aggregation
Inhibition of gamma-secretase expressed in CHO cells expressing human recombinant APP assessed as amyloid beta40 aggregation
|
[PMID: 19012391] |
Clinical Trial
| NCT Number | Sponsor | Condition | Start Date |
Phase
|
|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 443989-01-3
-
분자량 311.85
-
화학식 C11H18ClNO3S2
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SMILES
O=S(C1=CC=C(S1)Cl)(N[C@H](CO)C(CC)CC)=O
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선적
Room temperature in continental US; may vary elsewhere.
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보관
Please store the product under the recommended conditions in the Certificate of Analysis.
Protocol
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Cell Cytotoxicity Assay
Cytotoxicity assays are usually based on the assessment of cell membrane damage, which can also be indirectly detected by measuring cell viability. Detection methods include MTT assay, CKK-8 assay, LDH assay and ATP assay, etc.
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Notch Pathway Solutions
The Notch pathway is a contact-dependent signaling pathway that controls cell-fate decisions, differentiation, proliferation, and tissue patterning through interactions between membrane-bound Notch receptors and membrane-bound ligands on neighboring cells. Canonical Notch signaling is activated when ligand engagement triggers proteolytic release of the Notch intracellular domain, which enters the nucleus and regulates transcription together with DNA-binding transcriptional complexes. In the canonical mechanism, ligand-dependent Notch activation leads to release of the intracellular Notch domain, and presenilin-dependent γ-secretase activity is required for production of the active intracellular signaling fragment. The released intracellular domain functions as a nuclear signal that converts Notch receptor activation at the membrane into transcriptional regulation of target programs such as HES/HEY-family genes and other context-dependent downstream targets. The literature links Notch p
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Alzheimer’s Disease Modeling
Alzheimer’s Disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive functions and loss of specific types of neurons and synapses. Alzheimer's symptoms can be simulated in mice by injecting drugs (such as Aβ) or genetically modified.
순도&문서
References
[1]. Chinthakindi, P. K., et al., (2017). Sulfonimidamides in Medicinal and Agricultural Chemistry. Angewandte Chemie (International ed. in English), 56(15), 4100-4109. [Content Brief]
[2]. Sehgelmeble, F., et al., (2012). Sulfonimidamides as sulfonamides bioisosteres: rational evaluation through synthetic, in vitro, and in vivo studies with γ-secretase inhibitors. ChemMedChem, 7(3), 396-399. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)