EAI045 - Moligand™, 10mM in DMSO , Allosteric modulator of epidermal growth factor receptor, CAS No.1942114-09-1, Allosteric modulator of epidermal growth factor receptor

CAS: 1942114-09-1 Cat. No.: E422370 Summenformel: C₁₉H₁₄FN₃O₃S Molekulargewicht: 383.4

QUALITÄT & REINHEIT Moligand™, 10mM in DMSO

Synonyms

2H-​Isoindole-​2-​acetamide,α-​(5-​fluoro-​2-​hydroxyphenyl)​-​1,​3-​dihydro-​1-​oxo-​N-​2-​thiazolyl-

Storage

Store at -80°C

Shipped In

Dry ice packs + Cold packs

Übersicht

Information

EAI045 EAI045 is an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild-type receptor.

Targets

EGFR mutants

In vitro

EAI045 potently inhibits EGFR Y1173 phosphorylation in H1975 cells (half maximal effective concentration (EC50)=2nM), but not in HaCaT cells, a keratinocyte cell line with wild-type EGFR. Despite potent inhibition of mutant EGFR, EAI045 shows no anti-proliferative effect in the H1975 and H3255 cell lines with concentrations as high as 10μM. EAI045 inhibits L858R/T790M mutant with an IC50 of 3 nM. However, EAI045 is not able to completely abolish EGFR autophosphorylation in H1975 NSCLC cell line harboring the L858R/T790M mutant. Dimerization-defective/independent mutants are markedly more sensitive to EAI045. Since EGFR dimerization is required for kinase enzyme activation, EAI045 may be active against one subunit of an EGFR heterodimer/asymmetric dimer.

In vivo

Mouse pharmacokinetic studies with EAI045 reveals a maximal plasma concentration of 0.57μM, a half-life of 2.15 h, and oral bioavailability of 26% after dosing at 20mg/kg. When combined with cetuximab that blocks EGFR dimerization, EAI045 markedly reduces tumor growth in a mouse model of L858R/T790M-mutant-driven lung cancer. The mice treated alone with EAI045 do not respond. EAI045 in combination with cetuximab also induces marked tumor shrinkage in the mouse model carrying L858R/T790M/C797S, a mutant known to be resistant to all third-generation EGFR TKIs. EAI045 and cetuximab exhibits mechanistic synergy.

Cell Research(from reference)

Cell lines：H1975, H3255 and HaCaT cell lines 

Concentrations：Serial dilution (0-100 μM) 

Incubation Time：3 days 

Spezifikationen

Synonyme

2H-​Isoindole-​2-​acetamide,α-​(5-​fluoro-​2-​hydroxyphenyl)​-​1,​3-​dihydro-​1-​oxo-​N-​2-​thiazolyl-

Spezifikationen & Reinheit

Moligand™, 10mM in DMSO

Biochemische und physiologische Mechanismen

EAI045 is an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild-type receptor.

Storage

Store at -80°C

Verschickt in

Dry ice packs + Cold packs

Dieses Produkt erfordert Kühlkettenversand. Grundversand und andere Economy-Optionen sind nicht verfügbar.

Note

Moligand™

Aktionsart

ALLOSTERIC MODULATOR

Mechanismus der Wirkung

Allosteric modulator of epidermal growth factor receptor

Namen und Kennungen

Pubchem Sid

528764332

Pubchem Sid Url

https://pubchem.ncbi.nlm.nih.gov/substance/528764332

Kanonisches Lächeln

C1C2=CC=CC=C2C(=O)N1C(C3=C(C=CC(=C3)F)O)C(=O)NC4=NC=CS4

IUPAC Name

2-(5-fluoro-2-hydroxyphenyl)-2-(3-oxo-1H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)acetamide

InChIKey

YTUFHOKUFOQRDF-UHFFFAOYSA-N

INCHI

1S/C19H14FN3O3S/c20-12-5-6-15(24)14(9-12)16(17(25)22-19-21-7-8-27-19)23-10-11-3-1-2-4-13(11)18(23)26/h1-9,16,24H,10H2,(H,21,22,25)

Isomere SMILES

C1C2=CC=CC=C2C(=O)N1C(C3=C(C=CC(=C3)F)O)C(=O)NC4=NC=CS4

MeSH-Eintrag

2-(5-fluoro-2-hydroxyphenyl)-2-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)acetamide;EAI045

Molekulargewicht

383.4

Reaxy-Rn

33071410

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=33071410&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Klasse Isoindoles and derivatives
      • Subclass Isoindolines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Klasse: Isoindoles and derivatives
• Subclass: Isoindolines
• Intermediate Tree Nodes: Not available
• Direct Parent: Isoindolones
• Alternative Parents: Phenylacetamides Alpha amino acids and derivatives Isoindoles P-fluorophenols N-arylamides Fluorobenzenes 1-hydroxy-2-unsubstituted benzenoids Aryl fluorides Thiazoles Tertiary carboxylic acid amides Heteroaromatic compounds Secondary carboxylic acid amides Lactams Azacyclic compounds Organopnictogen compounds Organofluorides Organic oxides Hydrocarbon derivatives Carbonyl compounds
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Phenylacetamide - Isoindolone - Alpha-amino acid or derivatives - Isoindole - N-arylamide - 4-fluorophenol - 4-halophenol - 1-hydroxy-2-unsubstituted benzenoid - Phenol - Halobenzene - Fluorobenzene - Benzenoid - Monocyclic benzene moiety - Aryl halide - Aryl fluoride - Heteroaromatic compound - Thiazole - Tertiary carboxylic acid amide - Azole - Secondary carboxylic acid amide - Lactam - Carboxamide group - Azacycle - Carboxylic acid derivative - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Organic oxide - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Carbonyl group - Aromatic heteropolycyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as isoindolones. These are aromatic polycyclic compounds that an isoindole bearing a ketone.
• 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

Zugehörige Ziele (menschlich)

EGFR Tclin Epidermal growth factor receptor (2 Activities)

Discover Target: EGFR

Activity Type	Activity Value -log(M)	Mechanism of Action	Activity Reference	Publications (PubMed IDs)

EGFR Tclin Epidermal growth factor receptor erbB1 (33727 Activities)

Discover Target: EGFR

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Zugehörige Ziele (nicht menschlich)

BaF3 (4657 Activities)

Explore this target

Activity Type	Relation	Activity value	Units	Action Type	Journal	PubMed Id	doi	Assay Aladdin ID

Wirkungsmechanismen

Chemische und physikalische Eigenschaften

• Molekulargewicht: 383.400 g/mol
• XLogP3: 2.700
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 6
• Rotatable Bond Count: 4
• Exact Mass: 383.074 Da
• Monoisotopic Mass: 383.074 Da
• Topological Polar Surface Area: 111.000 Ų
• Heavy Atom Count: 27
• Formal Charge: 0
• Complexity: 580.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 1
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1