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| Targets |
MS9427 TFA targets the epidermal growth factor receptor (EGFR). It is a PROTAC that binds to EGFR via a warhead and simultaneously recruits an E3 ubiquitin ligase, leading to ubiquitination and subsequent proteasomal degradation of the EGFR protein. It selectively degrades mutant EGFR but not wild-type EGFR.
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| ln Vitro |
On HCC-827 cells, MS9427 TFA exhibits anti-proliferative action with a GI50 of 0.87 ± 0.27 μM [1]. In HCC-827 cells, MS9427 TFA (0-10μM, 16 h) consistently and concentration-dependently triggers EGFRdel19 degradation (DC50=82 ± 73 nM) and suppresses EGFR phosphorylation (p-EGFR) [1].
MS9427 TFA exhibits high binding affinities for EGFR with Kd values of 7.1 nM for wild-type EGFR and 4.3 nM for the L858R mutant EGFR. It shows anti-proliferative activity against HCC-827 NSCLC cells with a GI50 of 0.87 +/- 0.27 microM. It strongly inhibits NSCLC cell proliferation, induces selective degradation of mutant EGFR via both the ubiquitin-proteasome system (UPS) and autophagy-lysosome pathways. |
| Enzyme Assay |
A standard in vitro binding assay involves measuring the dissociation constant (Kd) of MS9427 TFA for EGFR using surface plasmon resonance (SPR) or a fluorescence polarization-based competition binding assay. Recombinant EGFR proteins (wild-type or L858R mutant) are immobilized, and varying concentrations of MS9427 TFA (0.1-1000 nM) are flowed over the chip. Binding responses are recorded to calculate Kd values (7.1 nM for wild-type, 4.3 nM for L858R).
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: HCC-827 cells Tested Concentrations: 1, 10, 50, 100, 200, 500, 100, and 10000 nM Incubation Duration: 16 h Experimental Results: Inhibited EGFR phosphorylation(p-EGFR) in a concentration -dependent manner in HCC-827 cells. Western Blot Analysis[1] Cell Types: HCC-827 cells Tested Concentrations: 100 nM Incubation Duration: 1, 2, 4, 6, 12, 24, 48 h Experimental Results: Induced EGFR degradation in a time-dependent manner and through the UPS and autophagy/lysosome system. A standard cellular protocol for assessing EGFR degradation involves treating HCC-827 or other EGFR-mutant NSCLC cells with MS9427 TFA at varying concentrations (0.01-10 microM) for 6-24 hours. After treatment, cells are lysed and analyzed by Western blotting using anti-EGFR and anti-tubulin (loading control) antibodies. The extent of EGFR protein degradation is quantified by densitometry. To validate degradation pathway, cells are co-treated with proteasome inhibitor (MG-132) or lysosome inhibitor (chloroquine). Cell proliferation is measured using MTT or CellTiter-Glo assays after 72 hours to determine GI50 values. |
| Animal Protocol |
Not available. For in vivo evaluation of MS9427 TFA, standard protocols would involve establishing subcutaneous NSCLC xenografts in nude mice using EGFR-mutant cell lines (e.g., HCC-827). Mice are treated with MS9427 TFA (e.g., 10-50 mg/kg) by intraperitoneal or intravenous injection daily or every other day for 2-4 weeks. Tumor volume is measured twice weekly, and at endpoint, tumors are excised for analysis of EGFR protein levels by immunohistochemistry and Western blotting.
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| ADME/Pharmacokinetics |
MS9427 TFA has a molecular weight of 1107.50 (C50H59ClF4N8O14) and purity >98%. For in vitro use, it is soluble in DMSO to prepare stock solutions. For in vivo formulation, standard co-solvent systems (e.g., 10% DMSO, 40% PEG300, 5% Tween-80, 45% saline) or liposomal formulations can be used. Powder form should be stored at -20degC for up to 3 years, and solution at -20degC for up to 6 months.
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| Toxicity/Toxicokinetics |
Specific toxicological data for MS9427 TFA is not available. As a PROTAC degrader, its toxicity would be determined by target selectivity and off-target degradation. The compound is designed to selectively degrade mutant EGFR over wild-type, which may reduce on-target toxicity in normal tissues. However, comprehensive toxicology studies have not been published.
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| References | |
| Additional Infomation |
MS9427 TFA is a research-grade PROTAC EGFR degrader. It represents a novel approach to targeting EGFR-driven cancers by inducing protein degradation rather than simple kinase inhibition. The compound degrades EGFR through dual pathways (UPS and autophagy-lysosome), which may overcome resistance mechanisms associated with kinase inhibitors. It has not been approved for clinical use and is strictly for laboratory research.
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| Molecular Formula |
C50H59CLF4N8O14
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| Molecular Weight |
1107.50
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| Related CAS # |
MS9427;2772613-37-1
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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 | 0.9029 mL | 4.5147 mL | 9.0293 mL | |
| 5 mM | 0.1806 mL | 0.9029 mL | 1.8059 mL | |
| 10 mM | 0.0903 mL | 0.4515 mL | 0.9029 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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