1. JAK/STAT Signaling
    Protein Tyrosine Kinase/RTK
  2. EGFR

EAI045 

Cat. No.: HY-100213 Purity: 99.33%
Data Sheet SDS Handling Instructions

EAI045 is an allosteric inhibitor of mutant EGFR with IC50s of 1.9, 0.019, 0.19 and 0.002 μM for EGFR, EGFRL858R, EGFRT790M and EGFRL858R/T790M at 10 μM ATP, respectively.

For research use only. We do not sell to patients.
EAI045 Chemical Structure

EAI045 Chemical Structure

CAS No. : 1942114-09-1

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10 mM * 1 mL in DMSO $77 In-stock
5 mg $70 In-stock
10 mg $90 In-stock
50 mg $260 In-stock
100 mg $450 In-stock
200 mg $750 In-stock
500 mg $1300 In-stock
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Customer Review

  • Biological Activity

  • Protocol

  • Technical Information

  • Purity & Documentation

  • References

Description

EAI045 is an allosteric inhibitor of mutant EGFR with IC50s of 1.9, 0.019, 0.19 and 0.002 μM for EGFR, EGFRL858R, EGFRT790M and EGFRL858R/T790M at 10 μM ATP, respectively.

IC50 & Target

IC50: 1.9 μM (EGFR), 0.019 μM (EGFRL858R), 0.19 μM (EGFRT790M), 0.002 μM (EGFRL858R/T790M)[1]

In Vitro

EAI045 potently inhibits EGFR Y1173 phosphorylation in H1975 cells (EC50=2 nM), but not in HaCaT cells. EAI045 is an inhibitor of the L858R/T790M mutant with 1000-fold selectivity versus wild type EGFR at 1 mM ATP. Profiling of EAI045 against a panel of 250 protein kinases reveals exquisite selectivity; no other kinases are inhibited by more than 20% at 1 μM EAI045[1]. EAI045 has high potency and selectivity for L858R/T790M mutation. In L858R/T790M-mutant NSCLC cell line H1975 cells, EAI045 decreases but does not completely abolish the EGFR autophosphorylation. In stably transfected NIH-3T3 cells harboring the L858R/T790M EGFR mutant, EAI045 shows the same activity. In L858R-mutant H3255 cells, EAI045 exhibits moderate activity. In the HaCaT cells, a keratinocyte cell line with wild-type EGFR, EAI045 does not show any activity of inhibiting EGFR phosphorylation. It confirms the selectivity of EAI045 for mutant EGFR[2].

In Vivo

In a genetically engineered mouse model of L858R/T790Mmutant-driven lung cancer , remarkable tumor regression is observed in L858R/T790M-mutant mice treated with the combination of EAI045 and cetuximab. No response is seen in those mice treated with EAI045 alone. The same effect is seen in both L858R/T790M/C797S- engineered Ba/F3 cells and in mice carrying the L858R/T790M/C797S tumor xenografts. These assays clearly show that EAI045 can overcome resistance from acquired T790M and C797S mutations[2].

References
Preparing Stock Solutions
Concentration Volume Mass 1 mg 5 mg 10 mg
1 mM 2.6082 mL 13.0412 mL 26.0824 mL
5 mM 0.5216 mL 2.6082 mL 5.2165 mL
10 mM 0.2608 mL 1.3041 mL 2.6082 mL
Please refer to the solubility information to select the appropriate solvent.
Cell Assay
[1]

For the experiment studying the effect of EGF pre-treatment on EAI045 target modulation, H1975 cells are harvested and plated in 0.5% FBS/RPMI Pen/Strep. On the following day, cells are pre-treated with 0.5% FBS/RPMI media with or without 10 ng EGF/mL for 5 minutes. Compound is added and assay is carried out[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration
[1]

The EAI045 compound is dissolved in 10% NMP (10% 1-methyl-2-pyrrolidinone: 90% PEG-300), and is dosed at 60 mg/kg daily by oral gavage[1].

Mouse: Cetuximab is administrated at 1 mg/mouse every other day by intraperitoneal injection. The TL, TD and TLCS mice are monitored by MRI to quantify lung tumor burden before being assigned to various study treatment cohorts, which are non-blinded and not formally randomized. All treated mice had an equal initial tumor burden. MRI evaluation is repeated every 2 weeks during treatment. The animals are imaged with a rapid acquisition with relaxation enhancement sequence in the coronal and axial planes with a 1-mm slice thickness gating with respiratory rates. The tumor burden volumes are quantified[1]. MCE has not independently confirmed the accuracy of these methods. They are for reference only.

References
Molecular Weight

383.4

Formula

C₁₉H₁₄FN₃O₃S

CAS No.

1942114-09-1

Storage
Powder -20°C 3 years
  4°C 2 years
In solvent -80°C 6 months
  -20°C 1 month
Shipping

Room temperature in continental US; may vary elsewhere

Solvent & Solubility

DMSO: ≥ 28 mg/mL

* "<1 mg/mL" means slightly soluble or insoluble. "≥" means soluble, but saturation unknown.

Purity: 99.33%

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Product Name:
EAI045
Cat. No.:
HY-100213
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