EAI045

SKU: orb1300432

Description

EAI045 is a selective allosteric inhibitor that potently targets drug-resistant EGFR mutants while sparing the wild-type receptor. It is a valuable chemical probe for studying resistance mechanisms in non-small cell lung cancer (NSCLC) and has demonstrated efficacy in both cellular assays and in vivo models.

Research Area

Cardiovascular Research, Signal Transduction

Key Properties

• CAS Number: 1942114-09-1
• MW: 383.4
• Purity: 99.73% (May vary between batches)
• Formula: C₁₉H₁₄FN₃O₃S
• SMILES: Oc1ccc(F)cc1C(N1Cc2ccccc2C1=O)C(=O)Nc1nccs1
• Target: EGFR
• Solubility: Ethanol:< 1 mg/mL (insoluble or slightly soluble);DMSO:16.67 mg/mL (43.48 mM);H2O:< 1 mg/mL (insoluble or slightly soluble);10% DMSO+40% PEG300+5% Tween 80+45% Saline:2 mg/mL (5.22 mM)

Bioactivity

• Target IC50:
  EGFR (L858R):0.002 μM|EGFR (L858R):0.019 μM|EGFR:1.9 μM|EGFR (T790M):0.19 μM
• In Vivo:
  Mouse pharmacokinetic studies with EAI045 reveals a maximal plasma concentration of 0.57 μM, a half-life of 2.15 h, and oral bioavailability of 26% after dosing at 20 mg/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.
• In Vitro:
  EAI045 potently inhibits EGFR Y1173 phosphorylation in H1975 cells (half maximal effective concentration (EC50)=2 nM) but not in HaCaT cells, which have wild-type EGFR. It shows no anti-proliferative effect in H1975 and H3255 cell lines even at concentrations up to 10 μM. EAI045 inhibits the L858R/T790M mutant with an IC50 of 3 nM but does not completely abolish EGFR autophosphorylation in H1975 NSCLC cells harboring this mutant. Dimerization-defective/independent mutants are more sensitive to EAI045, suggesting activity against one subunit of an EGFR heterodimer/asymmetric dimer.
• Cell Research:
  H1975, H3255 and HaCaT cell lines are plated in solid white 384-well plates at 500 cells per well in 10% FBS RPMI penicillin/streptomycin media. Using a Pin Tool, 50 nl of serial diluted compounds are transferred to the cells. After 3 days, cell viability is measured.(Only for Reference)

Storage & Handling

• Storage: Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice/Shipping at ambient temperature.
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Alternative Names

EAI 045, EAI045, EAI-045, HER1, EGFR, EGFR mutants, ErbB-1, Epidermal growth factor receptor, inhibit, Inhibitor

Compound Identifiers

PubChem CID

121231412