Compound E - Moligand™, ≥99% , CAS No.209986-17-4

CAS: 209986-17-4 Cat. No.: C275008 Molecular Weight: 490.50

GRADE & PURITY Moligand™, ≥99%

Synonyms

E98743 | BS-15830 | N-[(1S)-2-[[(3S)-2,3-Dihydro-1-methyl-2-oxo-5-phenyl-1H-1,4-benzodiazepin-3-yl]amino]-1-methyl-2-oxoethyl]-3,5-difluorobenzeneacetamide | EX-A3838 | CHEBI:131161 | C27H24F2N4O3 | GSI-XXI | Compound E | gamma-Secretase Inhibitor XXI | H

Storage

Protected from light,Store at -20°C,Desiccated

Shipped In

Ice chest + Ice pads

Overview

Compound E is a γ-secretase inhibitor. Compound E blocks β-amyloid(40), β-amyloid(42), and Notch γ-secretase cleavage with IC50s of 0.24, 0.37, 0.32 nM, respectively.A cell-permeable, potent, selective, peptidomimetic, non-transition-state analog inhibitor of γ-secretase and Notch processing (IC50 = 300 pM for Aβ40 in CHO cells overexpressing wild type βAPP; 240 pM for Aβ40, 370 pM for Aβ42, and 320 pM for NICD, respectively, in HEK293 cells stably transfected with βAPP695 and mNotchΔE(M1727V); 100 pM for both Aβ40 and Aβ42 in SH-SY5Y cells stably transfected with SPA4CT). Lowers Aβ levels in several APP transgenic mouse models. Reported to bind to presenilins and suppress the proteolytic cleavage of transmembrane protein substrates, including APLP1 and APLP2, CD44, ErbB4, E-cadherin, low density lipoprotein receptor-related proteins, Notch ligands, and p75NTR. Only weakly affects presenilinase activity at much higher concentrations (200-400 µM).

Specifications

Synonyms

E98743 | BS-15830 | N-[(1S)-2-[[(3S)-2, 3-Dihydro-1-methyl-2-oxo-5-phenyl-1H-1, 4-benzodiazepin-3-yl]amino]-1-methyl-2-oxoethyl]-3, 5-difluorobenzeneacetamide | EX-A3838 | CHEBI:131161 | C27H24F2N4O3 | GSI-XXI | Compound E | gamma-Secretase Inhibitor XXI | H

Specifications & Purity

Moligand™, ≥99%

Biochemical and Physiological Mechanisms

Cell-permeable, selective, non-competitive, potent γ-secretase inhibitor (IC 50 = 0.3 nM). Active in vitro and in vivo .

Storage

Protected from light, Store at -20°C, Desiccated

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Grade

Moligand™

Action Type

INHIBITOR

Note

Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20°C. Generally, these will be useable for up to one month. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room temperature for at least 1 hour. Need more advice on solubility, usage and handling? Please visit our frequently asked questions (FAQ) page for more details.

Purity

≥99%

Names and Identifiers

• Canonical Smiles: Fc1cc(cc(c1)CC(=O)N[C@@H](C)C(=O)NC2N=C(c4c(cccc4)N(C2=O)C)c3ccccc3)F
• IUPAC Name: (2S)-2-[[2-(3,5-difluorophenyl)acetyl]amino]-N-[(3S)-1-methyl-2-oxo-5-phenyl-3H-1,4-benzodiazepin-3-yl]propanamide
• InChIKey: JNGZXGGOCLZBFB-IVCQMTBJSA-N
• INCHI: 1S/C27H24F2N4O3/c1-16(30-23(34)14-17-12-19(28)15-20(29)13-17)26(35)32-25-27(36)33(2)22-11-7-6-10-21(22)24(31-25)18-8-4-3-5-9-18/h3-13,15-16,25H,14H2,1-2H3,(H,30,34)(H,32,35)/t16-,25+/m0/s1
• Isomeric SMILES: C[C@@H](C(=O)N[C@@H]1C(=O)N(C2=CC=CC=C2C(=N1)C3=CC=CC=C3)C)NC(=O)CC4=CC(=CC(=C4)F)F
• Molecular Weight: 490.50
• Reaxy-Rn: 24842893
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=24842893&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic acids and derivatives
    • Class Carboxylic acids and derivatives
      • Subclass Amino acids, peptides, and analogues
        • Level5 Peptides
          • Level6 Dipeptides

• Kingdom: Organic compounds
• Superclass: Organic acids and derivatives
• Class: Carboxylic acids and derivatives
• Subclass: Amino acids, peptides, and analogues
• Intermediate Tree Nodes: Peptides
• Direct Parent: Dipeptides
• Alternative Parents: N-acyl-alpha amino acids and derivatives Alpha amino acid amides 1,4-benzodiazepines Alanine and derivatives Phenylacetamides Fluorobenzenes Aryl fluorides Tertiary carboxylic acid amides Secondary carboxylic acid amides Lactams Ketimines Propargyl-type 1,3-dipolar organic compounds Azacyclic compounds Organopnictogen compounds Organic oxides Organofluorides Carbonyl compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Alpha-dipeptide - N-acyl-alpha amino acid or derivatives - Alpha-amino acid amide - Alanine or derivatives - 1,4-benzodiazepine - Benzodiazepine - N-substituted-alpha-amino acid - Alpha-amino acid or derivatives - Phenylacetamide - Fluorobenzene - Halobenzene - Aryl fluoride - Aryl halide - Monocyclic benzene moiety - Benzenoid - Tertiary carboxylic acid amide - Carboxamide group - Ketimine - Lactam - Secondary carboxylic acid amide - Propargyl-type 1,3-dipolar organic compound - Organic 1,3-dipolar compound - Organoheterocyclic compound - Azacycle - Organopnictogen compound - Organic oxygen compound - Imine - Organic nitrogen compound - Carbonyl group - Hydrocarbon derivative - Organic oxide - Organohalogen compound - Organofluoride - Organonitrogen compound - Organooxygen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as dipeptides. These are organic compounds containing a sequence of exactly two alpha-amino acids joined by a peptide bond.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Mechanisms of Action

Chemical and Physical Properties

• Solubility: Soluble in DMSO to 100 mM
• Sensitivity: Light sensitive；Heat sensitive
• Molecular Weight: 490.500 g/mol
• XLogP3: 3.600
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 6
• Exact Mass: 490.182 Da
• Monoisotopic Mass: 490.182 Da
• Topological Polar Surface Area: 90.900 Ų
• Heavy Atom Count: 36
• Formal Charge: 0
• Complexity: 837.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 2
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1