DAPT   Click here for help

GtoPdb Ligand ID: 11363

Synonyms: gamma-Secretase Inhibitor IX | GSI-IX | LY-374973
Compound class: Synthetic organic
Comment: DAPT is a γ-secretase inhibitor [1] that is used experimentally to inhibit NOTCH pathway signalling. Chemically it is a modified di-peptide (IUPAC Condensed name Unk-Ala-Phg-OtBu).

DAPT is commercially available from our sponsors

2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 6
Hydrogen bond donors 2
Rotatable bonds 11
Topological polar surface area 84.5
Molecular weight 432.19
XLogP 3.84
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES O=C(N[C@H](C(=O)N[C@@H](c1ccccc1)C(=O)OC(C)(C)C)C)Cc1cc(F)cc(c1)F
Isomeric SMILES O=C(N[C@H](C(=O)N[C@@H](c1ccccc1)C(=O)OC(C)(C)C)C)Cc1cc(F)cc(c1)F
InChI InChI=1S/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
InChI Key DWJXYEABWRJFSP-XOBRGWDASA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Czerwinski A, Valenzuela F, Afonine P, Dauter M, Dauter Z. (2010)
N-{N-[2-(3,5-Difluorophenyl)acetyl]-(S)-alanyl}-(S)-phenylglycine tert-butyl ester (DAPT): an inhibitor of γ-secretase, revealing fine electronic and hydrogen-bonding features.
Acta Crystallogr C, 66 (Pt 12): o585-8. [PMID:21123889]
2. Dovey HF, John V, Anderson JP, Chen LZ, de Saint Andrieu P, Fang LY, Freedman SB, Folmer B, Goldbach E, Holsztynska EJ et al.. (2001)
Functional gamma-secretase inhibitors reduce beta-amyloid peptide levels in brain.
J Neurochem, 76 (1): 173-81. [PMID:11145990]
3. Iben LG, Olson RE, Balanda LA, Jayachandra S, Robertson BJ, Hay V, Corradi J, Prasad CV, Zaczek R, Albright CF et al.. (2007)
Signal peptide peptidase and gamma-secretase share equivalent inhibitor binding pharmacology.
J Biol Chem, 282 (51): 36829-36. [PMID:17932033]