| Size | Price | Stock | Qty |
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| 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. EMI48 is a potent inhibitor that blocks the activity of these two clinically relevant triple-mutant forms of EGFR, which are a primary cause of resistance to Osimertinib. |
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| ln Vitro |
EMI48 is useful in the study of drug-resistant non-small-cell lung cancer (NSCLC) linked with mutant EGFR since it suppresses both EGFR ex19del/T790M/C797S and EGFR L858R/T790M/C797S[1].
EMI48 is a selective inhibitor targeting the EGFR triple mutant. It displays greater potency toward mutant EGFR than its predecessor, EMI1, with inhibitory effects observed at 5 uM. It effectively targets and inhibits EGFR ex19del/T790M/C797S and L858R/T790M/C797S but has no effect on wild-type EGFR. |
| ln Vivo |
EMI48 can be used in the research of mutant EGFR-associated, drug-resistant non-small-cell lung cancer (NSCLC). By effectively inhibiting both C797S-bearing triple mutants, it provides a powerful research tool for studying the primary mechanism of resistance to Osimertinib. It is used to explore therapeutic strategies for resistant NSCLC.
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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 an ADP-Glo luminescence detection kit. IC50 values are calculated.
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| Cell Assay |
NSCLC cell lines engineered to express the EGFR triple mutants are seeded in 96-well plates. Cells are treated with increasing concentrations of EMI48 for 72 hours. Cell viability is measured using the CellTiter-Glo reagent. The inhibition of mutant EGFR phosphorylation is confirmed by Western blot using phospho-specific antibodies. Wild-type EGFR cells serve as a control.
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| Animal Protocol |
For in vivo studies, EMI48 would be administered to mice bearing xenografts of triple-mutant NSCLC cells. Dosing regimens are not specified. Tumor volumes would be measured with calipers. At study termination, tumors would be excised for pharmacodynamic analysis to confirm EGFR inhibition and assess downstream signaling markers.
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| ADME/Pharmacokinetics |
No specific PK data are reported for EMI48. The molecular weight is 348.4 (C21H20N2O3) and the CAS number is 34564-13-1. 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 and oral bioavailability have not been characterized. It is a research chemical.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for EMI48. Its selectivity for mutant EGFR over the wild-type receptor suggests a potentially improved safety profile in vivo. This compound is for research use only and is not intended for human use. Standard toxicological assessments have not been performed.
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| References |
[1]. Punit Saraon , et al. A Drug Discovery Platform to Identify Compounds That Inhibit EGFR Triple Mutants.Nat Chem Biol. 2020 May;16(5):577-586.
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| Additional Infomation |
Other information: EMI48 (CAS 34564-13-1) is a research compound, not FDA-approved. It is a potent, selective inhibitor of Osimertinib-resistant EGFR triple mutants. It exhibits greater potency than EMI1 and has no effect on wild-type EGFR. It is a valuable tool for studying drug resistance in NSCLC and for the development of fourth-generation EGFR inhibitors. For research use only.
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| Molecular Formula |
C21H20N2O3
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|---|---|
| Molecular Weight |
348.40
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| Exact Mass |
348.147
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| CAS # |
34564-13-1
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| PubChem CID |
15538560
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.755
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
560
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(N(CC)C1C=CC2C=C(C3=NC4C=C(C)C=CC=4O3)C(=O)OC=2C=1)C
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| InChi Key |
PTAGJQADNFQMGR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H20N2O3/c1-4-23(5-2)15-8-7-14-11-16(21(24)26-19(14)12-15)20-22-17-10-13(3)6-9-18(17)25-20/h6-12H,4-5H2,1-3H3
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| Chemical Name |
7-(diethylamino)-3-(5-methyl-1,3-benzoxazol-2-yl)chromen-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: 9.26 mg/mL (26.58 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (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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