| Size | Price | Stock | Qty |
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| 100mg |
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| 500mg |
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| Targets |
EGFR-IN-8 is a dual inhibitor of the epidermal growth factor receptor (EGFR) and c-Met (HGFR). It simultaneously targets both receptor tyrosine kinases, which are frequently co-activated in EGFR TKI-resistant NSCLC, thereby blocking multiple oncogenic signaling pathways.
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| ln Vitro |
In A549, PC9, H1975, CL68, and CL97 cells, EGFR-IN-8 (0–20 μM; 24-72 hours) exhibited time- and dose-dependent inhibitory effects at various time intervals; after 72 hours and 72 hours, respectively, the IC50 values ranged from 48 from 0.3 to 0.6μM and 0.2–0.5μM[1]. Whatever the mutational state of these five cell lines, EGFR-IN-8 (0-0.6 μM; 48 hours) suppresses EGFR and c-Met expression [1].
EGFR-IN-8 inhibits EGFR and c-Met expression in A549, PC9, H1975, CL68, and CL97 cell lines at concentrations ranging from 0 to 0.6 μM over 48 hours. The inhibitory effect is independent of the mutation status of the cells, suggesting broad activity against various NSCLC subtypes. The compound demonstrates antiproliferative activity across multiple cancer cell lines. |
| ln Vivo |
EGFR-IN-8 (oral gavage; 50 and 150 mg/kg; once daily; 20 days) demonstrated dose-dependent inhibition of H1975 xenograft tumor growth at doses of 50 and 150 mg/kg (29%, respectively and 60%). 1].
In vivo, EGFR-IN-8 (50 mg/kg and 150 mg/kg; oral gavage) exhibits dose-dependent suppression of H1975 xenograft tumor growth, with tumor growth inhibition of 29% and 60%, respectively. These results indicate that EGFR-IN-8 has significant antitumor efficacy in preclinical models of EGFR TKI-resistant NSCLC. |
| Enzyme Assay |
Biochemical assays for EGFR-IN-8 typically involve kinase activity measurements using recombinant EGFR and c-Met enzymes. The compound is incubated with the kinase, ATP, and a peptide substrate. Phosphorylation of the substrate is detected using fluorescence or luminescence-based methods. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Cell viability assay [1]
Cell Types: A549, PC9, H1975, CL68, CL97 Cell Tested Concentrations: 0-20 μM Incubation Duration: 24 hrs (hours), 48 hrs (hours), 72 hrs (hours) Experimental Results: Inhibitory effect on different cells. Western Blot Analysis[1] Cell Types: A549, PC9, H1975, CL68 and CL97 Cell Tested Concentrations: 0-0.6 μM Incubation Duration: 48 hrs (hours) Experimental Results: diminished EGFR and c-Met expression. In vitro cellular assays for EGFR-IN-8 are performed using NSCLC cell lines including A549, PC9, H1975, CL68, and CL97. Cells are treated with the compound (0-0.6 μM) for 48 hours, and EGFR and c-Met expression levels are assessed by Western blotting. Cell viability and proliferation are measured using MTT or CCK-8 assays. |
| Animal Protocol |
Animal/Disease Models: Nude mouse H1975 xenograft tumor model [1]
Doses: 50 and 150 mg/kg Route of Administration: po (oral gavage); 50 and 150 mg/kg; one time/day; 20 days Experimental Results: Inhibition of H1975 xenograft tumor growth. In vivo efficacy studies of EGFR-IN-8 are conducted using H1975 xenograft tumor models in immunodeficient mice. Tumor-bearing mice are administered the compound via oral gavage at doses of 50 mg/kg and 150 mg/kg. Tumor volumes are measured at regular intervals using calipers to assess growth inhibition. Body weight is monitored to evaluate tolerability. |
| ADME/Pharmacokinetics |
Pharmacokinetic properties of EGFR-IN-8 are evaluated in rodents following oral administration. The compound is typically formulated in appropriate vehicles (e.g., 0.5% methylcellulose or PEG-based solutions). Plasma concentrations are measured using LC-MS/MS to determine key PK parameters including Cmax, Tmax, half-life, and oral bioavailability.
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| Toxicity/Toxicokinetics |
EGFR-IN-8 is intended for research use only and is not approved for clinical use. Standard toxicology studies would include acute and repeat-dose toxicity assessments in rodents, as well as safety pharmacology evaluations. No specific toxicity data is available in the public domain for this compound.
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| References | |
| Additional Infomation |
EGFR-IN-8 is a dual EGFR/c-Met inhibitor designed to address the challenge of acquired resistance to first-generation EGFR TKIs in NSCLC. By simultaneously targeting both EGFR and c-Met, it has the potential to overcome resistance mechanisms including MET amplification and T790M mutations. The compound represents a promising lead for the development of next-generation therapies for EGFR TKI-resistant NSCLC.
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| Molecular Formula |
C32H23CLF3N7O4
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|---|---|
| Molecular Weight |
662.017735719681
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| Exact Mass |
661.15
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| Elemental Analysis |
C, 58.06; H, 3.50; Cl, 5.35; F, 8.61; N, 14.81; O, 9.67
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| CAS # |
2407957-87-1
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| PubChem CID |
139035057
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
4.9
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
8
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| Heavy Atom Count |
47
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| Complexity |
1120
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1C=C(C=CC=1C1=NOC(C2=CC=CC(=C2)NC(NC2C=CC(=C(C(F)(F)F)C=2)NC(C2CC2)=O)=O)=N1)NC(C1C=NC=CC=1)=O
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| InChi Key |
IIUNSVLRVWGJRM-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C32H23ClF3N7O4/c33-25-15-22(38-29(45)19-4-2-12-37-16-19)8-10-23(25)27-42-30(47-43-27)18-3-1-5-20(13-18)39-31(46)40-21-9-11-26(24(14-21)32(34,35)36)41-28(44)17-6-7-17/h1-5,8-17H,6-7H2,(H,38,45)(H,41,44)(H2,39,40,46)
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| Chemical Name |
N-(3-chloro-4-(5-(3-(3-(4-(cyclopropanecarboxamido)-3-(trifluoromethyl)phenyl)ureido)phenyl)-1,2,4-oxadiazol-3-yl)phenyl)nicotinamide
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| Synonyms |
EGFR-IN-8; 2407957-87-1; starbld0000884; CHEMBL4443455; EX-A7176; AKOS040733075; AC-36780
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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 : ~8.33 mg/mL (~12.58 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 | 1.5105 mL | 7.5526 mL | 15.1053 mL | |
| 5 mM | 0.3021 mL | 1.5105 mL | 3.0211 mL | |
| 10 mM | 0.1511 mL | 0.7553 mL | 1.5105 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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