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| Targets |
PROTAC EGFR degrader 7 targets the EGFRL858R/T790M double mutant form of the epidermal growth factor receptor (EGFR). This mutant is associated with acquired resistance to first- and second-generation EGFR tyrosine kinase inhibitors (TKIs) in non-small cell lung cancer (NSCLC). The compound is a PROTAC that recruits the E3 ubiquitin ligase Cereblon (CRBN) via its CRBN-binding moiety. It induces ubiquitination and proteasomal degradation of the EGFRL858R/T790M mutant protein.
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| ln Vitro |
In vitro, PROTAC EGFR degrader 7 diTFA is a potent and selective CRBN-recruiting EGFRL858R/T790M degrader with a DC50 of 13.2 nM. It effectively inhibits NCI-H1975 cell proliferation with an IC50 of 46.82 nM. The compound significantly induces apoptosis and G2/M phase arrest in NCI-H1975 cells. It shows antitumor activity and can be used for non-small cell lung cancer (NSCLC) research. The diTFA salt enhances solubility.
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| ln Vivo |
In vivo, PROTAC EGFR degrader 7 diTFA shows antitumor activity and can be used for non-small cell lung cancer (NSCLC) research. It is a CRBN-recruiting PROTAC degrader targeting EGFRL858R/T790M. The compound can degrade the mutant EGFR protein in vivo, leading to tumor growth inhibition. Detailed in vivo efficacy data (e.g., tumor xenograft models, dosing regimens) are not provided in the available search results.
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| Enzyme Assay |
A cell-free binding assay for PROTAC EGFR degrader 7 is not typical; degradation activity requires the ubiquitin-proteasome system in living cells. For target engagement studies, SPR can be used to measure binding of the EGFR ligand to purified EGFRL858R/T790M protein. For CRBN engagement, a TR-FRET-based competition assay with recombinant CRBN and a fluorescent thalidomide probe can be performed. The full PROTAC's activity is assessed in cell-based degradation assays.
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| Cell Assay |
NCI-H1975 NSCLC cells (which harbor the EGFRL858R/T790M double mutation) are seeded in 96-well plates in RPMI-1640 + 10% FBS. After overnight incubation, cells are treated with PROTAC EGFR degrader 7 diTFA at varying concentrations (0.1-1000 nM) for 48-72 hours. Cell viability is measured by MTT or CellTiter-Glo to determine the IC50 (46.82 nM). For degradation assays, cells are treated for 6-24 hours, and EGFR protein levels are assessed by Western blot to determine the DC50 (13.2 nM). Apoptosis is assessed by Annexin V/PI staining and flow cytometry. Cell cycle analysis is performed by propidium iodide staining.
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| Animal Protocol |
PROTAC EGFR degrader 7 diTFA can be studied in mouse xenograft models of NSCLC. Female BALB/c nude mice are implanted subcutaneously with NCI-H1975 cells (5×10⁶ cells in 100 uL PBS/Matrigel). When tumors reach 100-150 mm3, mice are randomized into groups (n=6-8 per group). PROTAC EGFR degrader 7 diTFA (10-50 mg/kg) is dissolved in a vehicle (10% DMSO + 40% PEG300 + 5% Tween 80 + 45% saline) and administered intraperitoneally or orally. Tumor volume is measured every 2-3 days. EGFR degradation in tumors is confirmed by Western blot.
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| ADME/Pharmacokinetics |
PROTAC EGFR degrader 7 diTFA has a molecular weight of 1064.98 and the molecular formula C50H50F6N10O10. The product should be stored at -20degC in a sealed container, protected from moisture and light. In solvent, it is stable for 6 months at -80degC or 1 month at -20degC. The diTFA salt enhances solubility in aqueous buffers. Specific PK parameters have not been reported. The compound is soluble in DMSO. For in vivo use, it requires formulation with a suitable vehicle.
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| Toxicity/Toxicokinetics |
No detailed toxicity data for PROTAC EGFR degrader 7 diTFA are available. As a research-grade PROTAC, it is used at low concentrations in vitro and in vivo. The compound targets the EGFRL858R/T790M mutant, which is primarily expressed in cancer cells, reducing the risk of on-target toxicity in normal tissues. However, formal toxicology studies have not been conducted. Standard safety precautions for handling PROTAC molecules and chemical compounds should be followed.
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| References | |
| Additional Infomation |
PROTAC EGFR degrader 7 diTFA (compound 13b) is a research-grade PROTAC and is not approved for clinical use. It is a potent, selective, CRBN-recruiting EGFRL858R/T790M degrader with a DC50 of 13.2 nM. It inhibits NCI-H1975 cell proliferation with an IC50 of 46.82 nM and shows antitumor activity. This compound is a valuable research tool for studying acquired resistance to EGFR-TKIs in NSCLC. It is for research use only.
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| Molecular Formula |
C50H50F6N10O10
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| Molecular Weight |
1064.98
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| Appearance |
Light yellow to yellow solid powder
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.9390 mL | 4.6949 mL | 9.3898 mL | |
| 5 mM | 0.1878 mL | 0.9390 mL | 1.8780 mL | |
| 10 mM | 0.0939 mL | 0.4695 mL | 0.9390 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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