| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
EGFR (wild-type and mutant forms). BAY 2476568 is a selective and potent EGFR inhibitor with IC50 values <0.2 nM for wild-type EGFR and various exon 20 insertion mutants (insASV, insSVD, insNPG).
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| ln Vitro |
BAY 2476568 potently inhibits the kinase activity of both wild-type EGFR (IC50 <0.2 nM) and several EGFR exon 20 insertion mutants, with IC50 values of 0.09 nM (insASV), 0.21 nM (insSVD), and 0.11 nM (insNPG). It is designed to overcome resistance to first- and second-generation EGFR inhibitors.
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| ln Vivo |
BAY 2476568 is a research tool with potent activity against EGFR exon 20 insertion mutations, which are typically resistant to standard EGFR inhibitors. In cellular assays, it inhibits EGFR phosphorylation and reduces the phosphorylation of downstream signaling molecules ERK1/2 and Akt, demonstrating its in vitro efficacy in overcoming resistance.
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| Enzyme Assay |
Cell-free EGFR kinase assays are performed using recombinant human wild-type EGFR and various mutant EGFR proteins (e.g., insASV, insSVD, insNPG). 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 or a TR-FRET assay. IC50 values (<0.2 nM) are calculated.
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| Cell Assay |
Ba/F3 cells engineered to express EGFR exon 20 insertion mutants (e.g., insASV, insSVD) are seeded in 96-well plates. Cells are treated with increasing concentrations of BAY 2476568 for 72 hours. Cell viability is assessed by the CellTiter-Glo reagent. The inhibition of EGFR phosphorylation (Y1068) and downstream ERK1/2 and Akt (S473) is measured by Western blot.
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| Animal Protocol |
No specific in vivo animal protocols are published for BAY 2476568. For potential in vivo studies, it would be administered orally to mice bearing xenografts of EGFR exon 20 insertion mutant-driven tumors. Tumor volumes would be measured with calipers. At termination, tumors would be collected for Western blot analysis of EGFR, ERK, and Akt phosphorylation.
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| ADME/Pharmacokinetics |
No specific pharmacokinetic data are reported for BAY 2476568. The molecular weight is 425.35 (C21H20F2N6OS). It is soluble in DMSO (100 mg/mL). For in vivo studies, it would typically be formulated in a vehicle such as 0.5% methylcellulose or a DMSO/PEG300/Tween-80/saline mixture. Its half-life, oral bioavailability, and metabolism have not been characterized.
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| Toxicity/Toxicokinetics |
No specific toxicity data are reported for BAY 2476568. As a highly potent pan-EGFR inhibitor, on-target toxicity may include dose-limiting adverse events typical of EGFR inhibitors, such as skin rash and gastrointestinal effects. However, its high potency against resistant mutants suggests it might be effective at lower, potentially safer doses.
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| References | |
| Additional Infomation |
Other information: BAY 2476568 (CAS 2311901-93-4) is a research-grade chemical, not an FDA-approved drug. It is a highly selective and efficient EGFR inhibitor (IC50 <0.2 nM) that targets both wild-type and clinically relevant exon 20 insertion mutants. It is a valuable tool for developing targeted therapies for resistant NSCLC. For research use only.
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| Molecular Formula |
C24H27FN4O4
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|---|---|
| Molecular Weight |
454.49
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| Exact Mass |
454.201
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| CAS # |
2311901-93-4
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| PubChem CID |
142566590
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
3.3
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
7
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
33
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| Complexity |
668
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1(=O)NCCC2NC(C3C=CN=CC=3OCC(OC)(C)C)=C(NC3=CC=CC(F)=C3OC)C1=2
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| InChi Key |
ZOEVXMKZJWZLFX-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H27FN4O4/c1-24(2,32-4)13-33-18-12-26-10-8-14(18)20-21(19-16(28-20)9-11-27-23(19)30)29-17-7-5-6-15(25)22(17)31-3/h5-8,10,12,28-29H,9,11,13H2,1-4H3,(H,27,30)
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| Chemical Name |
3-(3-fluoro-2-methoxyanilino)-2-[3-(2-methoxy-2-methylpropoxy)pyridin-4-yl]-1,5,6,7-tetrahydropyrrolo[3,2-c]pyridin-4-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: 100 mg/mL (220.03 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 | 2.2003 mL | 11.0013 mL | 22.0027 mL | |
| 5 mM | 0.4401 mL | 2.2003 mL | 4.4005 mL | |
| 10 mM | 0.2200 mL | 1.1001 mL | 2.2003 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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