| 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. |
|---|---|
| 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) |
DMSO: ~100 mg/mL (~194.6 mM; with ultrasonication)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (4.86 mM) in 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 400 μL of PEG300 and mix well; then add 50 μL of Tween-80 and mix well; finally add 450 μL of physiological saline and 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 (4.86 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), Clear solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of DMSO stock solution (25.0 mg/mL) to 900 μL of corn oil and mix well. (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.
Products are for research use only; We do not sell to patients
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