| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| Other Sizes |
| Targets |
EGFR (ErbB1) and HER2 (ErbB2). Mefatinib is an irreversible dual inhibitor with an IC50 of 0.4 nM for EGFR and 11.7 nM for HER2. It forms a covalent bond with a cysteine residue in the ATP-binding pocket of these receptors.
|
|---|---|
| ln Vitro |
Mefatinib inhibits EGFR with an IC50 of 0.4 nM, which is equipotent or superior to afatinib (0.5 nM). It maintains comparable HER2 inhibitory activity (11.7 nM vs. 14 nM for afatinib). In vitro, it blocks the proliferation of EGFR-mutant NSCLC cell lines and HER2-amplified breast cancer cells, inducing apoptosis and G1 cell cycle arrest.
|
| ln Vivo |
In mouse xenograft models of EGFR-mutant NSCLC, oral administration of Mefatinib induces significant and dose-dependent tumor regression. It has shown superiority over first-generation reversible EGFR inhibitors in models of acquired resistance. Its irreversible binding mechanism provides sustained target inhibition and a long duration of action.
|
| Enzyme Assay |
Cell-free kinase assays are performed using recombinant human EGFR and HER2 enzymes. The compound is pre-incubated with the enzyme for 10-15 minutes to allow for covalent binding. Then, ATP and a peptide substrate are added. After 30-60 minutes, the reaction is quenched, and IC50 values are measured using an ADP-Glo luminescence detection kit.
|
| Cell Assay |
EGFR-mutant NSCLC cell lines (e.g., PC-9, HCC827) or HER2-amplified cells (e.g., NCI-N87) are seeded in 96-well plates and treated with Mefatinib for 72 hours. Cell viability is measured using the CellTiter-Glo reagent. The effect on downstream signaling pathways (p-EGFR, p-AKT, p-ERK) is measured by Western blot. Apoptosis is assessed by Caspase-3/7 activity.
|
| Animal Protocol |
To assess in vivo efficacy, a NSCLC xenograft model is established in BALB/c nude mice by subcutaneous inoculation of EGFR-mutant cells. When tumors reach a certain volume, mice are treated orally with Mefatinib (10-50 mg/kg) once daily. Tumor volumes are measured with calipers twice weekly. At study termination, tumors are excised for pharmacodynamic analysis of EGFR phosphorylation.
|
| ADME/Pharmacokinetics |
Mefatinib is orally bioavailable and has favorable pharmacokinetic properties for cancer treatment. Its irreversible binding mechanism supports once-daily oral dosing. The free base form is critical for its solubility and absorption. It is metabolized in the liver, primarily by CYP3A4, and has a moderate terminal half-life in preclinical species.
|
| Toxicity/Toxicokinetics |
No specific toxicity data are detailed. As an irreversible EGFR/HER2 inhibitor, its safety profile is expected to be similar to other drugs in its class (e.g., Afatinib), with potential adverse events including diarrhea, skin rash, and stomatitis. In preclinical studies, it was generally well-tolerated, with no significant off-target toxicities reported.
|
| References | |
| Additional Infomation |
Other information: Mefatinib free base (CAS 1639014-72-4) is a research compound. It is distinct from the dimaleate salt form. Its irreversible inhibition of both EGFR and HER2 makes it a valuable tool for studying mechanisms of resistance to reversible inhibitors. It is not FDA-approved and is strictly for research use only. Synonyms: Mifanertinib.
|
| Molecular Formula |
C21H19CLF3N5O2
|
|---|---|
| Molecular Weight |
465.856073617935
|
| Exact Mass |
465.117
|
| CAS # |
1639014-72-4
|
| Related CAS # |
Mefatinib;1989592-50-8;Mefatinib-d6
|
| PubChem CID |
71613550
|
| Appearance |
White to off-white solid powder
|
| LogP |
4.5
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
9
|
| Rotatable Bond Count |
8
|
| Heavy Atom Count |
32
|
| Complexity |
645
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(NC1C(OC(F)F)=CC2C(C=1)=C(NC1=CC=C(F)C(Cl)=C1)N=CN=2)(=O)/C=C/CN(C)C
|
| InChi Key |
QPACRWFSFWQNOZ-ONEGZZNKSA-N
|
| InChi Code |
InChI=1S/C21H19ClF3N5O2/c1-30(2)7-3-4-19(31)29-17-9-13-16(10-18(17)32-21(24)25)26-11-27-20(13)28-12-5-6-15(23)14(22)8-12/h3-6,8-11,21H,7H2,1-2H3,(H,29,31)(H,26,27,28)/b4-3+
|
| Chemical Name |
(E)-N-[4-(3-chloro-4-fluoroanilino)-7-(difluoromethoxy)quinazolin-6-yl]-4-(dimethylamino)but-2-enamide
|
| HS Tariff Code |
2934.99.9001
|
| 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) |
DMSO: ≥ 50 mg/mL (107.33 mM)
|
|---|---|
| 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 | 2.1466 mL | 10.7328 mL | 21.4657 mL | |
| 5 mM | 0.4293 mL | 2.1466 mL | 4.2931 mL | |
| 10 mM | 0.2147 mL | 1.0733 mL | 2.1466 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
