| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
EGFRL858R/T790M/C797S EGFRdel19 T790M C797S
EGFR triple mutants: ex19del/T790M/C797S and L858R/T790M/C797S. EMI56 is a mutant-selective inhibitor that simultaneously blocks the activity of these two clinically relevant triple-mutant forms of EGFR. |
|---|---|
| ln Vitro |
EMI56 can be employed in the study of drug-resistant non-small-cell lung cancer (NSCLC) linked with mutant EGFR since it inhibits both EGFR ex19del/T790M/C797S and EGFR L858R/T790M/C797S[1]. PC9 EGFR ex19del/T790M/C797S cells exhibit substantial inhibition of total EGFR levels, activation, and downstream signaling under treatment with EMI56 (10, 15, 20 μM) for two hours[1].
EMI56 inhibits both EGFR ex19del/T790M/C797S and EGFR L858R/T790M/C797S, which are resistance mechanisms to third-generation EGFR inhibitors. It is a derivative of EMI1 and exhibits stronger effects on mutant EGFR than its predecessor, making it a potent tool for targeting Osimertinib-resistant NSCLC. |
| ln Vivo |
EMI56 can be employed in the study of drug-resistant non-small-cell lung cancer (NSCLC) linked with mutant EGFR. By inhibiting the two major C797S-bearing triple mutants, it provides a research avenue for overcoming the primary resistance mechanism to Osimertinib. Its in vivo efficacy is under investigation.
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| Enzyme Assay |
Cell-free EGFR kinase assays are performed using recombinant EGFR triple mutant proteins (ex19del/T790M/C797S and L858R/T790M/C797S). The compound is incubated with the enzyme and a peptide substrate in the presence of ATP for 30-60 minutes. Kinase activity is measured using a luminescence-based ADP detection kit, and IC50 values are calculated.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: PC9 EGFR ex19del/T790M/C797S cells Tested Concentrations: 1, 5, 10, 15, 20 μM Incubation Duration: 2 hrs (hours) Experimental Results: Inhibited total EGFR levels from 10 μM concentration. NSCLC cell lines engineered to express the EGFR triple mutants are seeded in 96-well plates and treated with increasing concentrations of EMI56 for 72 hours. Cell viability is measured using the CellTiter-Glo reagent. The inhibition of EGFR phosphorylation is confirmed by Western blot using phospho-specific antibodies. |
| Animal Protocol |
For in vivo studies, EMI56 would be administered to mice bearing xenografts of triple-mutant NSCLC cells. Dosing regimens are not specified but would likely be oral once daily. Tumor volumes would be measured with calipers. At study termination, tumors would be excised for pharmacodynamic analysis of EGFR and downstream signaling.
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| ADME/Pharmacokinetics |
No specific PK data are reported for EMI56. The molecular weight is 348.40 (C21H20N2O3). It is soluble in DMSO (50 mg/mL). For in vivo studies, it would be formulated in a vehicle such as 0.5% methylcellulose. Its half-life, oral bioavailability, and clearance have not been characterized. It is a research-grade chemical.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for EMI56. As a selective mutant EGFR inhibitor, its potential to cause off-target toxicities is expected to be lower than that of pan-EGFR inhibitors. This compound is for research use only and is not an FDA-approved drug. Comprehensive toxicology studies have not been performed.
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| References | |
| Additional Infomation |
Other information: EMI56 (CAS 2414374-41-5) is a research compound, not FDA-approved. It is a potent inhibitor of the Osimertinib-resistant EGFR ex19del/T790M/C797S and L858R/T790M/C797S triple mutants. It is a valuable tool for developing new therapies for drug-resistant NSCLC. For research use only.
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| Molecular Formula |
C21H20N2O3
|
|---|---|
| Molecular Weight |
348.395105361938
|
| Exact Mass |
348.147
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| CAS # |
2414374-41-5
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| PubChem CID |
145864056
|
| Appearance |
Yellow to orange solid powder
|
| LogP |
4.6
|
| Hydrogen Bond Donor Count |
0
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
4
|
| Heavy Atom Count |
26
|
| Complexity |
560
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| Defined Atom Stereocenter Count |
0
|
| SMILES |
O1C(C(C2=NC3C=CC=CC=3O2)=CC2C=C(C)C(=CC1=2)N(CC)CC)=O
|
| InChi Key |
OYQNORRYAWXDHW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H20N2O3/c1-4-23(5-2)17-12-19-14(10-13(17)3)11-15(21(24)26-19)20-22-16-8-6-7-9-18(16)25-20/h6-12H,4-5H2,1-3H3
|
| Chemical Name |
3-(1,3-benzoxazol-2-yl)-7-(diethylamino)-6-methylchromen-2-one
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: 50 mg/mL (143.51 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (5.97 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 sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.8703 mL | 14.3513 mL | 28.7026 mL | |
| 5 mM | 0.5741 mL | 2.8703 mL | 5.7405 mL | |
| 10 mM | 0.2870 mL | 1.4351 mL | 2.8703 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.
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