| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 100mg | |||
| Other Sizes |
| Targets |
The primary target of SJFδ is the p38δ protein, a member of the p38 MAP kinase family. It acts as a PROTAC by simultaneously binding to p38δ and the E3 ubiquitin ligase VHL. This brings the target protein into proximity with the ubiquitin-proteasome system, leading to its ubiquitination and subsequent degradation. SJFδ is highly selective, degrading p38δ with a DC50 of 46.17 nM while sparing p38α, p38β, and p38γ.
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| ln Vitro |
In vitro, SJFδ selectively degrades p38δ protein in a concentration-dependent manner. The degradation is mediated by the VHL E3 ligase pathway. Its selectivity for p38δ over other p38 isoforms makes it a powerful tool for dissecting the specific biological functions of p38δ without off-target effects on other family members. The compound's activity is assessed by measuring the reduction in p38δ protein levels via Western blot, with a DC50 of 46.17 nM.
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| ln Vivo |
In vivo efficacy data for SJFδ are limited. As a PROTAC, its activity is expected to translate to in vivo models, but specific studies have not been detailed. The compound's large molecular weight (1168.27) may pose challenges for oral bioavailability, but it could be administered via intraperitoneal or intravenous injection. Further studies would be required to establish its in vivo pharmacokinetics, efficacy, and safety profile.
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| Enzyme Assay |
For cellular degradation assays, cells expressing p38δ are cultured in appropriate medium. They are treated with varying concentrations of SJFδ for a specified time. Cells are then lysed, and protein levels are analyzed by Western blot using anti-p38δ and anti-p38 (pan) antibodies. Degradation efficiency is quantified by densitometry, and the DC50 is calculated. For selectivity, the levels of other p38 isoforms are also assessed.
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| Cell Assay |
For cellular studies, cells are seeded in 6-well or 96-well plates and treated with SJFδ at concentrations ranging from 1 nM to 10 µM for 4-24 hours. Cells are lysed in RIPA buffer with protease inhibitors. Target protein levels are analyzed by Western blot. Cell viability is assessed by MTT or CellTiter-Glo assays after 48-72 hours of treatment. Apoptosis is assessed by Annexin V/PI staining.
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| Animal Protocol |
For in vivo efficacy studies, 6-8 week old female immunodeficient mice could be used. Mice would be subcutaneously implanted with cancer cells. When tumors reach approximately 100-200 mm³, animals are randomized into treatment groups. SJFδ is formulated in vehicle and administered intravenously or intraperitoneally. Tumor volumes are measured twice weekly. At study termination, tumors are excised and processed for Western blot analysis of p38δ degradation.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of SJFδ are not extensively reported. As a large PROTAC molecule (MW 1168.27), it is expected to have poor oral bioavailability and would likely require parenteral administration. Its pharmacokinetic profile, including half-life, clearance, and tissue distribution, would need to be characterized for any therapeutic development. The linker and ligand composition are designed for PROTAC function.
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| Toxicity/Toxicokinetics |
Toxicological data for SJFδ are limited, as it is a research compound. No acute toxicity, organ-specific toxicity, or mutagenicity data have been reported. As with all research compounds, appropriate safety precautions should be taken when handling SJFδ, including the use of personal protective equipment.
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| References | |
| Additional Infomation |
SJFδ (CAS 2254609-23-7) is a PROTAC that selectively degrades p38δ with a DC50 of 46.17 nM. It is based on a VHL ligand and has a 10-atom linker. It does not degrade p38α, p38β, or p38γ. Its molecular formula is C₆₂H₆₃F₂N₇O₁₂S, and its molecular weight is 1168.27. It is a valuable tool for studying p38δ biology and is strictly for research use.
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| Molecular Formula |
C62H63F2N7O12S
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|---|---|
| Molecular Weight |
1168.26514172554
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| Exact Mass |
1119.458
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| CAS # |
2254609-23-7
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| PubChem CID |
155885775
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
7.4
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
16
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| Rotatable Bond Count |
27
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| Heavy Atom Count |
80
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| Complexity |
2030
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
CGOWEGDPCPSDKZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C59H67F2N7O11S/c1-36-52(80-35-65-36)38-12-10-37(11-13-38)32-64-54(71)46-29-42(69)33-67(46)55(72)53(58(2,3)4)66-51(70)34-77-26-7-6-24-76-25-8-9-27-78-50-31-45-43(30-49(50)75-5)47(20-23-63-45)79-48-19-18-41(28-44(48)61)68(40-16-14-39(60)15-17-40)57(74)59(21-22-59)56(62)73/h10-20,23,28,30-31,35,42,46,53,69H,6-9,21-22,24-27,29,32-34H2,1-5H3,(H2,62,73)(H,64,71)(H,66,70)
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| Chemical Name |
1-N'-[3-fluoro-4-[7-[4-[4-[2-[[1-[4-hydroxy-2-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methylcarbamoyl]pyrrolidin-1-yl]-3,3-dimethyl-1-oxobutan-2-yl]amino]-2-oxoethoxy]butoxy]butoxy]-6-methoxyquinolin-4-yl]oxyphenyl]-1-N'-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide
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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) |
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 | 0.8560 mL | 4.2798 mL | 8.5597 mL | |
| 5 mM | 0.1712 mL | 0.8560 mL | 1.7119 mL | |
| 10 mM | 0.0856 mL | 0.4280 mL | 0.8560 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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