208255-80-5

Basic information

• Product Name: DAPT
• Synonyms: LY-374973, N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-S-phenylglycine t-butyl ester;γ-Secretase Inhibitor IX;N-[(3,5-Difluorophenyl)acetyl]-L-alanyl-2-phenyl]glycine-1,1-dimethylethylester;SC-201315;(2S)-N-[N-(3,5-Difluorophenacetyl)-L-alanyl]-2-phenylglycine tert-butyl ester;DAPT (enzyme inhibitor);GSI-IX;DAPT (GSI-IX)
• CAS NO: 208255-80-5
• Molecular Formula: C₂₃H₂₆F₂N₂O₄
• Molecular Weight: 432.464
• Product Categories: Angiogenesis and Metastasis;Protease inhibitor;Inhibitor;GSI-IX;Inhibitors
• Mol File: 208255-80-5.mol
• Article Data: 3

Chemical Properties

• Boiling Point: 612.2 °C at 760 mmHg
• Flash Point: 324.1 °C
• Appearance: white/solid
• Density: 1.213
• Vapor Pressure: 6.31E-15mmHg at 25°C
• Refractive Index: 1.534
• Storage Temp.: 2-8°C
• Solubility: DMSO: ~18 mg/mL
• PKA: 12.82±0.46(Predicted)
• Sensitive: Light Sensitive
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20° for up to 3 months.
• CAS DataBase Reference: DAPT(CAS DataBase Reference)
• NIST Chemistry Reference: DAPT(208255-80-5)
• EPA Substance Registry System: DAPT(208255-80-5)

Safety Data

• Safety Statements: 24/25
• WGK Germany: 3
• Hazardous Substances Data: 208255-80-5(Hazardous Substances Data)

Usage

Description

DAPT (208255-80-5) is an inhibitor of γ-secretase (IC50 in human primary neurons = 115 nM for total Aβ or 200 nM for Aβ42 specifically).1?Oral administration of DAPT has been shown to reduce levels of Aβ in brain extract, cerebrospinal fluid and plasma from mice and rats.2,3?DAPT blocks Notch signaling which promotes neuronal differentiation of precursor cells.4?Enhances iPS cells without oncogenes KLF4 and CMYC5. Cell permeable.

Uses

Different sources of media describe the Uses of 208255-80-5 differently. You can refer to the following data:
1. DAPT (GSI-IX) is a novel γ-secretase inhibitor, which inhibits Aβ production with IC50 of 20 nM in HEK 293 cells
2. A potent and specific inhibitor of γ-secretase.
3. DAPT is used in the study of β-amyloid formation. DAPT has been shown to inhibit Notch signaling in studies of autoimmune and lymphoproliferative diseases, such as ALPS and lupus erythematosus, as well as in cancer cell growth, angiogenesis, and differentiation of human induced pluripotent stem cells.

Biological Activity

Inhibitor of γ -secretase; causes a reduction in A β 40 and A β 42 levels in human primary neuronal cultures (IC 50 values are 115 and 200 nM for total A β and A β 42 respectively) and in brain extract, cerebrospinal fluid and plasma in vivo . Does not effect APP α and APP β levels. Blocks Notch signaling in hybrid human-mouse foetal thymus organ culture (FTOC). Activity causes neural cells to commit to neuronal differentiation.

Biochem/physiol Actions

DAPT is a γ-secretase inhibitor and indirectly an inhibitor of Notch, a γ-secretase substrate. Other γ-secretase substrates include LDL receptor-related protein, E-cadherin and ErbB-4. As an inhibitor of γ-secretase, DAPT may be useful in the study of β-amyloid (Aβ) formation. DAPT has been shown to inhibit Notch signaling in studies of autoimmune and lymphoproliferative diseases, such as ALPS and lupus erythematosus (SLE), as well as in cancer cell growth, angiogenesis, and differentiation of human induced pluripotent stem cells (hIPSC).

References

1) Dovey?et al. (2001),?Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain; J. Neurochem.,?76?173 2) Portelius?et al. (2009),?Effects of γ-secretase inhibition on the amyloid β isoform pattern in a mouse model of Alzheimer’s disease; Cell Signal.,?5?615 3) El Moueddon?et al. (2006),?Reduction of Aβ levels in the Sprague Dawley rat after oral administration of the functional γ-secretase inhibitor, DAPT: a novel non-transgenic model for Aβ production inhibitors; Curr. Pharma. Des.,?12?1671 4) De Smedt?et al. (2005), Different thresholds of notch signaling bias human precursor cells towards B-, NK-, monocytic/dendritic, or T-cell lineage in thymus microenvironment; Blood,?106?2236 5) Ichida?et al. (2014),?Notch inhibition allows oncogene-independent generation of iPS cells; Nature Chem. Biol.,?10?632

InChI:InChI=1/C23H26F2N2O4/c1-14(26-19(28)12-15-10-17(24)13-18(25)11-15)21(29)27-20(16-8-6-5-7-9-16)22(30)31-23(2,3)4/h5-11,13-14,20H,12H2,1-4H3,(H,26,28)(H,27,29)/t14-,20-/m0/s1

Upstream product

• 53934-78-4 (S)-2-amino-2-phenylacetic acid tert-butyl ester 
• 2935-35-5 (S)-2-phenylglycine 
• 860013-16-7 N-(N-carbobenzyloxy-L-alanyl)-(2S)-2-phenylglycine tert-butyl ester 
• 105184-38-1 3,5-difluorophenyl acetic acid 
• 327052-53-9 N-(L-alanyl)-(2S)-2-phenylglycine tert-butyl ester 

Downstream Products

• 263162-50-1 (2S)-({N-[(3,5-difluorophenyl)acetyl]-L-alanyl}amino)(phenyl)acetic acid 

Relevant articles and documents

Design of β-secretase inhibitors by introduction of a mandelyl moiety in DAPT analogues

We report the synthesis of two series of compounds with 3,5-difluoromandelyl-alanyl or 3,5-difluorophenylacetylalany1 backbones coupled to various heterocyclic or peptidic moieties. These two series of compounds were evaluated for their inhibitory propert

Parallel synthesis of DAPT derivatives and their γ-secretase- inhibitory activity

Parallel synthesis of the C-terminal-modified DAPT (1) derivatives was accomplished utilizing our novel resin 7. Condensation reaction of the N-acylamino acid 10 with the amines 11a-o proceeded smoothly to give the corresponding amides 6a-o without any epimerization. Among the analogues, the benzophenonemethyl amide derivative 6o showed 30 times more potent activity than the original DAPT (1).