Size | Price | Stock | Qty |
---|---|---|---|
10mg |
|
||
25mg |
|
||
50mg |
|
||
100mg |
|
||
250mg |
|
||
Other Sizes |
|
Purity: =99.15%
EAI045 (EAI-045) is a 4th generation selective & allosteric EGFR inhibitor overcoming T790M and C797S resistance. It acts by targeting drug-resistant EGFR mutants but spares the wild-type receptor. It has IC50s of 1.9, 0.019, 0.19 and 0.002 μM for EGFR, EGFRL858R, EGFRT790M and EGFRL858R/T790M at 10 μM ATP, respectively. EAI1045 has an IC50 of 3 nM against the L858R/T790M mutant with a 1000-fold selectivity over wild-type EGFR at 1 mM ATP. In combination with 10 μg/ml cetuximab, EAI045 inhibited proliferation of EGFR (L858R/T790M) Ba/F3 cells with an IC50 of approximately 10nM. In mice treated with EAI045, combined treatment with cetuximab showed prominent tumour regressions, but these treated with EAI045 alone did not respond to the treatment.
ln Vitro |
EAI045, but not HaCaT cells, potently suppresses EGFR Y1173 phosphorylation in H1975 cells (EC50=2 nM). At 1 mM ATP, EAI045 is a 1000-fold selective inhibitor of the L858R/T790M mutant compared to wild-type EGFR. EAI045 exhibits remarkable selectivity when compared to a panel of 250 protein kinases; at 1 μM, no other kinase is inhibited by more than 20%[1]. High potency and selectivity are seen for the L858R/T790M mutation in EAI045. EAI045 reduces EGFR autophosphorylation in L858R/T790M-mutant NSCLC cell line H1975 cells, although it does not entirely eliminate it. EAI045 exhibits the same activity in stably transfected NIH-3T3 cells expressing the L858R/T790M EGFR mutation. EAI045 has moderate activity in H3255 cells carrying the L858R mutation. EAI045 does not exhibit any action of suppressing EGFR phosphorylation in the HaCaT cells, a keratinocyte cell line with wild-type EGFR. It validates EAI045's specificity for EGFR mutants[2].
|
||
---|---|---|---|
ln Vivo |
L858R/T790M-mutant mice treated with a combination of EAI045 and cetuximab showed remarkable tumor regression in a genetically engineered mouse model of L858R/T790Mmutant-driven lung cancer. In mice treated with EAI045 alone, there is no noticeable reaction. Both mice bearing the L858R/T790M/C797S tumor xenografts and Ba/F3 cells engineered with these mutations exhibit the same effect. These tests unequivocally demonstrate that acquired T790M and C797S mutation resistance can be overcome by EAI045[2].
|
||
Animal Protocol |
|
||
References |
[1]. Jia Y, et al. Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors. Nature. 2016 Jun 2;534(7605):129-32.
[2]. Wang S, et al. EAI045: The fourth-generation EGFR inhibitor overcoming T790M and C797S resistance. Cancer Lett. 2017 Jan 28;385:51-54 |
Molecular Formula |
C19H14FN3O3S
|
|
---|---|---|
Molecular Weight |
383.40
|
|
CAS # |
1942114-09-1
|
|
Related CAS # |
1942114-09-1;
|
|
SMILES |
O=C(NC1=NC=CS1)C(C2=CC(F)=CC=C2O)N3CC4=C(C=CC=C4)C3=O
|
|
Synonyms |
|
|
Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
Solubility (In Vitro) |
|
|||
---|---|---|---|---|
Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.52 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.5 mg/mL (6.52 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C,1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (6.52 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
Preparing Stock Solutions | 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration: mg/mL;
Method for preparing DMSO stock solution: mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation::Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O,mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
th> |
---|
td> |
td> |