DAPT A potent and specific inhibitor of γ-secretase

DAPT (CAS 208255-80-5)

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Sinónimo: Gamma-Secretase Inhibitor IX;N-[N-(3,5-Difluorophenacetyl-L-alanyl)]-S-phenylglycine t-butyl ester
Solicitud: A potent and specific inhibitor of γ-secretase
Número de CAS: 208255-80-5
Pureza: ≥95%
Peso Molecular: 432.46
Fórmula Molecular: C23H26F2N2O4
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DAPT is a potent and specific inhibitor of γ-secretase. It has been shown to cause a reduction in Aβ40 and Aβ42 levels in human primary neuronal cultures (IC50 values are 115 and 200 nM for total Aβ40 and Aβ42 respectively). There is evidence that DAPT does not effect APPα and APPβ levels. It mimics notch signaling deficiencies at morphological, molecular and biochemical levels and has been shown to block notch signaling in hybrid human-mouse foetal thymus organ culture (FTOC).


References

1. Dovey, H F., et al., 2001. Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain. Journal of neurochemistry. 76(1): 173-81. PMID: 11145990
2. Geling, Andrea., et al., 2002. A gamma-secretase inhibitor blocks Notch signaling in vivo and causes a severe neurogenic phenotype in zebrafish. EMBO reports. 3(7): 688-94. PMID: 12101103
3. Lanz, Thomas A., et al., 2003. The gamma-secretase inhibitor N-[N-(3,5-difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester reduces A beta levels in vivo in plasma and cerebrospinal fluid in young (plaque-free) and aged (plaque-bearing) Tg2576 mice. The Journal of pharmacology and experimental therapeutics. 305(3): 864-71. PMID: 12626636
4. Gowrishankar, Kavitha., et al., 2004. Release of a membrane-bound death domain by gamma-secretase processing of the p75NTR homolog NRADD. Journal of cell science. 117(Pt 18): 4099-111. PMID: 15280425
5. De Smedt, Magda., et al., 2005. Different thresholds of Notch signaling bias human precursor cells toward B-, NK-, monocytic/dendritic-, or T-cell lineage in thymus microenvironment. Blood. 106(10): 3498-506. PMID: 16030192
6. El Mouedden, Mohammed., et al., 2006. Reduction of Abeta levels in the Sprague Dawley rat after oral administration of the functional gamma-secretase inhibitor, DAPT: a novel non-transgenic model for Abeta production inhibitors. Current pharmaceutical design. 12(6): 671-6. PMID: 16472156

Uso :
DAPT is soluble in DMSO.
Apariencia :
Powder
Estado de Materia :
Solid
Solubilidad :
Soluble in DMSO (15 mg/mL), ethanol (~1 mg/mL), dichloromethane, DMF (~25 mg/mL), and 1:9 solution of DMF:PBS(pH 7.2) (~0.1 mg/mL).
ALMACENAMIENTO :
Store at -20° C
Punto de ebullición :
~612.2° C at 760 mmHg (Predicted)
Densidad :
~1.2 g/cm3 (Predicted)
Indice de Refracción :
n20D 1.53 (Predicted)
IC50 :
total Aβ: IC50 = 115 nM (human); Aβ42: IC50 = 200 nM (human)
Valores de pK :
pKa: 12.82 (Predicted)
Para Uso Exclusivo en Investigación. No está diseñado para uso en diagnosis o terapia.
WGK Alemania :
3
PubChem CID :
5311272
Número MDL :
MFCD04974585
SMILES :
C[C@@H](C(=O)N[C@@H](C1=CC=CC=C1)C(=O)OC(C)(C)C)NC(=O)CC2=CC(=CC(=C2)F)F

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DAPT  Menciones del Producto

Ver como otros han utilizado DAPT. Haga click en la entrada de PubMed .

Citaciones 1 a 10 de un total de 21

PMID: # 28771710  Lee, ML. et al. 2017. J. Neurochem.

PMID: # 26746659  Dinicola, S. et al. 2016. Life Sci. 145: 174-83.

PMID: # 26523864  Zhao, E. et al. 2016. Nat. Immunol. 17: 95-103.

PMID: # 26648098  Gao, Y. et al. 2016. International journal of oncology. 48: 281-92.

PMID: # 26067594  Wang, SY. et al. 2015. Neuroscience. 301: 276-88.

PMID: # 26355082  Kwon, YC. et al. 2015. J. Virol. 89: 11549-56.

PMID: # 26308963  Yu, L. et al. 2015. Journal of pineal research. 59: 420-33.

PMID: # 26534964  Londino, JD. et al. 2015. J. Biol. Chem. 290: 31113-25.

PMID: # 24881778  Richardson, T. et al. 2014. Tissue Eng Part A. 20: 3198-211.

PMID: # 23188126  You, J. et al. 2013. Journal of cardiovascular pharmacology. 61: 142-51.

Citaciones 1 a 10 de un total de 21
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