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Activity Type | Activity Value -log(M) | Mechanism of Action | Activity Reference | Publications (PubMed IDs) |
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SKU | Size | Availability | Price | Qty |
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E422370-1ml | 1ml | Available within 4-8 weeks(?) Items will be manufactured post-order and can take 4-8 weeks. Thank you for your patience! | $241.90 |
EGFR Inhibitors
Specifications & Purity | Moligand™, 10mM in DMSO |
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Biochemical and Physiological Mechanisms | EAI045 is an allosteric inhibitor that targets selected drug-resistant EGFR mutants but spares the wild-type receptor. |
Storage Temp | Store at -80°C |
Shipped In | Ice chest + Ice pads |
Grade | Moligand™ |
Product Description | 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 |
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IUPAC Name | 2-(5-fluoro-2-hydroxyphenyl)-2-(3-oxo-1H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)acetamide |
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INCHI | 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) |
InChi Key | YTUFHOKUFOQRDF-UHFFFAOYSA-N |
Canonical SMILES | C1C2=CC=CC=C2C(=O)N1C(C3=C(C=CC(=C3)F)O)C(=O)NC4=NC=CS4 |
Isomeric SMILES | C1C2=CC=CC=C2C(=O)N1C(C3=C(C=CC(=C3)F)O)C(=O)NC4=NC=CS4 |
PubChem CID | 121231412 |
MeSH Entry Terms | 2-(5-fluoro-2-hydroxyphenyl)-2-(1-oxo-2,3-dihydro-1H-isoindol-2-yl)-N-(1,3-thiazol-2-yl)acetamide;EAI045 |
Molecular Weight | 383.4 |
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