| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
EGFR 3.2 nM (IC50) EGFRT790M 8.3 nM (IC50) HER2 14 nM (IC50)
EGFR (ErbB1) and HER2 (ErbB2/Neu). EGFR/HER2-IN-9 is an irreversible dual inhibitor with IC50s of 3.2 nM (EGFR), 8.3 nM (EGFR T790M), and 14 nM (HER2). It forms a covalent bond with a cysteine residue in the ATP-binding pocket. |
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| ln Vitro |
EGFR/HER2-IN-9 is a potent inhibitor with IC50 values of 3.2 nM for wild-type EGFR, 8.3 nM for the drug-resistant EGFR T790M mutant, and 14 nM for HER2. Its dual inhibition profile and potency against the T790M mutant make it valuable for studying resistance to first-generation EGFR inhibitors in NSCLC.
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| ln Vivo |
EGFR/HER2-IN-9 exhibits anti-proliferative activity against EGFR- and HER2-driven cancer cells. Its ability to inhibit the EGFR T790M mutant at an IC50 of 8.3 nM suggests it may be effective in vivo against tumors that have developed resistance to gefitinib or erlotinib, making it a useful research tool for studying resistance mechanisms.
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| Enzyme Assay |
Cell-free EGFR, EGFR T790M, and HER2 kinase assays are performed using recombinant human enzymes. The compound is pre-incubated with the enzyme for 10-15 minutes to allow for covalent binding. Then, a peptide substrate and ATP are added. After 30-60 minutes, kinase activity is measured using a luminescence-based ADP detection kit. IC50 values are calculated.
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| Cell Assay |
EGFR-mutant NSCLC cell lines (e.g., HCC827, H1975 for T790M) or HER2-amplified cells (e.g., NCI-N87) are seeded in 96-well plates and treated with increasing concentrations of the compound for 72 hours. Cell viability is assessed by the MTT assay or CellTiter-Glo. The inhibition of EGFR and HER2 phosphorylation is measured by Western blot.
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| Animal Protocol |
For in vivo studies, the compound would be administered orally to mice bearing xenografts of EGFR T790M-mutant or HER2-driven tumors. Dosing regimens are not specified. Tumor volumes would be measured with calipers. At study termination, tumors would be excised for Western blot analysis of receptor phosphorylation and downstream signaling.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data are reported for EGFR/HER2-IN-9. The molecular weight is 513.95 (C25H25ClFN5O4). The compound is soluble in DMSO (10-50 mg/mL). For in vivo studies, it would typically be formulated in a vehicle such as 0.5% methylcellulose. Its half-life, oral bioavailability, and clearance have not been characterized. It is stored at -20degC.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for EGFR/HER2-IN-9. As an irreversible dual inhibitor, its safety profile is expected to be similar to that of other drugs in its class (e.g., Afatinib), with potential for gastrointestinal and dermatologic adverse events. The compound is for research use only and is not intended for human consumption.
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| References | |
| Additional Infomation |
Other information: EGFR/HER2-IN-9 (Compound 1, CAS 1637253-79-2) is a research compound and not FDA-approved. It is a potent, irreversible dual inhibitor with excellent potency against the clinically relevant EGFR T790M resistance mutation (IC50 = 8.3 nM). It is a valuable tool for drug discovery in NSCLC and HER2+ cancers. For research use only.
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| Exact Mass |
513.158
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|---|---|
| CAS # |
1637253-79-2
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| PubChem CID |
117685125
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| Appearance |
Off-white to light yellow solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
36
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| Complexity |
767
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| Defined Atom Stereocenter Count |
2
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| SMILES |
COC1=C(C=C2C(=C1)N=CN=C2NC3=CC(=C(C=C3)F)Cl)NC(=O)/C=C/CN4C[C@@H]5[C@H](C4)OCCO5
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| InChi Key |
REGOTSLWVKSZRG-GYQWKJCYSA-N
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| InChi Code |
InChI=1S/C25H25ClFN5O4/c1-34-21-11-19-16(25(29-14-28-19)30-15-4-5-18(27)17(26)9-15)10-20(21)31-24(33)3-2-6-32-12-22-23(13-32)36-8-7-35-22/h2-5,9-11,14,22-23H,6-8,12-13H2,1H3,(H,31,33)(H,28,29,30)/b3-2+/t22-,23+
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| Chemical Name |
(E)-4-[(4aR,7aS)-2,3,4a,5,7,7a-hexahydro-[1,4]dioxino[2,3-c]pyrrol-6-yl]-N-[4-(3-chloro-4-fluoroanilino)-7-methoxyquinazolin-6-yl]but-2-enamide
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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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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.) |
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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