| Targets |
SJF-1521 targets the epidermal growth factor receptor (EGFR) for degradation via the ubiquitin-proteasome pathway. As a PROTAC, it is a bifunctional molecule that simultaneously binds to EGFR and an E3 ubiquitin ligase, leading to the ubiquitination and subsequent proteasomal degradation of the EGFR protein. This mechanism is distinct from traditional kinase inhibition, as it removes the target protein entirely. It achieves selective degradation of EGFR while preserving the closely related HER2.
|
|---|---|
| ln Vitro |
In vitro, SJF-1521 induces significant degradation of EGFR in OVCAR8 cells. Its activity is characterized by its ability to lower cellular EGFR protein levels, which can be measured by Western blot. It is a selective EGFR degrader that does not affect HER2 levels. Specific quantitative activity data such as DC50 values are not detailed in the available literature, but its primary utility is as a tool for targeted protein degradation.
|
| ln Vivo |
In vivo activity data for SJF-1521 are not available in the current scientific literature. Its primary application remains as a research tool for in vitro studies of targeted protein degradation. As a PROTAC with a high molecular weight, its in vivo properties would need to be evaluated empirically.
|
| Enzyme Assay |
No specific in vitro enzyme or receptor binding assay protocols have been published for SJF-1521, as its mechanism is based on protein degradation rather than direct enzymatic inhibition. Standard protocols for assessing PROTAC activity typically involve Western blot analysis to measure the reduction of target protein levels. Cells are treated with varying concentrations of the compound, and EGFR protein levels are quantified and compared to loading controls.
|
| Cell Assay |
In vitro cell-based assay protocols for SJF-1521 involve treating cultured cells, such as the OVCAR8 cell line, with the compound to assess EGFR degradation. A standard protocol would involve seeding cells in multi-well plates, treating them with varying concentrations of SJF-1521 for a defined period (e.g., 4-24 hours), and then harvesting cells for protein extraction. The level of EGFR protein is then analyzed by Western blot.
|
| Animal Protocol |
No in vivo animal experimental protocols have been specifically established or reported for SJF-1521. The compound is primarily used for in vitro research, and no animal model studies have been described in the available literature.
|
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of SJF-1521 have not been characterized in any published studies. As a PROTAC with a large molecular weight (1074.65), it would be expected to have high polarity and potentially low oral bioavailability. Standard formulations for in vivo administration might include DMSO:PEG300:Tween 80:Saline, but specific PK parameters such as half-life, Cmax, and AUC have not been reported.
|
| Toxicity/Toxicokinetics |
Toxicological properties of SJF-1521 have not been systematically evaluated in any published studies. The compound is intended for research use only and is not for human therapeutic or diagnostic applications. As with all research chemicals, appropriate safety precautions, including working in a fume hood and wearing personal protective equipment, should be taken when handling this compound.
|
| References | |
| Additional Infomation |
SJF-1521 is a research-grade PROTAC molecule used for the targeted degradation of EGFR. It has not entered clinical trials and is not approved for any therapeutic indication. Its mechanism of action is based on inducing the degradation of EGFR via the ubiquitin-proteasome pathway. It is available exclusively for research purposes and is not intended for human use.
|
| Molecular Formula |
C57H61CLFN7O9S
|
|---|---|
| Molecular Weight |
1074.65
|
| Exact Mass |
1073.392
|
| CAS # |
2230821-40-4
|
| PubChem CID |
135157094
|
| Appearance |
Light green to yellow solid powder
|
| Density |
1.3±0.1 g/cm3
|
| Boiling Point |
1160.1±65.0 °C at 760 mmHg
|
| Flash Point |
655.4±34.3 °C
|
| Vapour Pressure |
0.0±0.3 mmHg at 25°C
|
| Index of Refraction |
1.629
|
| LogP |
7.54
|
| Hydrogen Bond Donor Count |
4
|
| Hydrogen Bond Acceptor Count |
15
|
| Rotatable Bond Count |
25
|
| Heavy Atom Count |
76
|
| Complexity |
1780
|
| Defined Atom Stereocenter Count |
3
|
| SMILES |
N(C1C=CC(OCC2C=CC=C(F)C=2)=C(Cl)C=1)C1=NC=NC2C=CC(C3C=CC(OCCOCCOCCOCC(=O)N[C@@H](C(C)(C)C)C(N4C[C@H](O)C[C@H]4C(=O)NCC4C=CC(C5SC=NC=5C)=CC=4)=O)=CC=3)=CC1=2
|
| InChi Key |
XZNORRXEBCTXPB-KHBXAZQSSA-N
|
| InChi Code |
InChI=1S/C57H61ClFN7O9S/c1-36-52(76-35-63-36)40-10-8-37(9-11-40)30-60-55(69)49-29-44(67)31-66(49)56(70)53(57(2,3)4)65-51(68)33-73-23-22-71-20-21-72-24-25-74-45-16-12-39(13-17-45)41-14-18-48-46(27-41)54(62-34-61-48)64-43-15-19-50(47(58)28-43)75-32-38-6-5-7-42(59)26-38/h5-19,26-28,34-35,44,49,53,67H,20-25,29-33H2,1-4H3,(H,60,69)(H,65,68)(H,61,62,64)/t44-,49+,53-/m1/s1
|
| Chemical Name |
(2S,4R)-1-[(2S)-2-[[2-[2-[2-[2-[4-[4-[3-chloro-4-[(3-fluorophenyl)methoxy]anilino]quinazolin-6-yl]phenoxy]ethoxy]ethoxy]ethoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]pyrrolidine-2-carboxamide
|
| HS Tariff Code |
2934.99.9001
|
| 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)
|
| Solubility (In Vitro) |
DMSO :~100 mg/mL (~93.05 mM; with heating and sonication.)
|
|---|---|
| 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 | 0.9305 mL | 4.6527 mL | 9.3054 mL | |
| 5 mM | 0.1861 mL | 0.9305 mL | 1.8611 mL | |
| 10 mM | 0.0931 mL | 0.4653 mL | 0.9305 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.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
