| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
cullin-RING ligases[1]
Skp2 (S-phase kinase-associated protein 2). Skp2 inhibitor 2 blocks the interaction between Skp2 and the Skp1-Cul1-F-box (SCF) complex, preventing ubiquitination and degradation of its substrates. It has an IC50 of 10.2 uM against the Skp2-Cks1 complex. |
|---|---|
| ln Vitro |
Skp2 inhibitor 2 (compound 14f) inhibits the Skp2-Cks1 complex with an IC50 of 10.2 uM. By blocking the Skp2-Cks1 interaction, it prevents the ubiquitination and subsequent degradation of p27Kip1, a key cell cycle inhibitor. This leads to the restoration of p27Kip1 levels, which results in G1 cell cycle arrest and reduced proliferation of cancer cells.
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| ln Vivo |
No detailed in vivo activity data for Skp2 inhibitor 2 are publicly available. However, as a Skp2 inhibitor, it is expected to suppress tumor growth in preclinical models of cancer where Skp2 is overexpressed, such as breast cancer, prostate cancer, and hepatocellular carcinoma. The compound has potential for anticancer research, particularly in restoring cell cycle control.
|
| Enzyme Assay |
To evaluate Skp2-Skp1 binding inhibition, a time-resolved fluorescence resonance energy transfer (TR-FRET) assay is commonly used. Biotinylated Skp1 and His-tagged Skp2-Cks1 are mixed with a europium-labeled anti-His antibody and streptavidin-allophycocyanin. Skp2 inhibitor 2 is added at varying concentrations. Upon light excitation at 320 nm, fluorescence is read at 615 nm and 665 nm. A decrease in the ratio indicates disruption of the Skp2-Skp1 interaction.
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| Cell Assay |
Cellular assays involve treating cancer cell lines (e.g., H1299 or MCF-7) with Skp2 inhibitor 2 at concentrations of 5-50 uM for 24-72 hours. Cell lysates are analyzed by Western blot for p27Kip1 accumulation, as well as cyclin E and CDK2 levels. Cell cycle distribution is assessed by propidium iodide staining and flow cytometry to confirm G1 arrest. Cell proliferation is measured by MTT or colony formation assays.
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| Animal Protocol |
For in vivo efficacy studies, the compound would be formulated in a vehicle such as 10% DMSO, 40% PEG300, 5% Tween-80, and 45% saline. It would be administered intraperitoneally or orally to tumor-bearing mice (e.g., H1299 xenografts) at doses of 10-50 mg/kg. Tumor volume is measured, and harvested tumors are analyzed for p27Kip1 levels by Western blot and immunohistochemistry.
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| ADME/Pharmacokinetics |
Soluble in DMSO up to 12 mg/mL (28 mM). For in vivo use, it can be formulated using 10% DMSO + 40% PEG300 + 5% Tween-80 + 45% saline. Storage: 4degC, sealed, away from moisture and light. The powder is stable for long-term storage at -20degC. Detailed PK parameters (half-life, bioavailability) are not extensively reported.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for Skp2 inhibitor 2 are not available. It is intended for research use only and not for human consumption. Standard laboratory safety precautions, including the use of gloves and eye protection, should be followed. The compound may be irritating to the skin, eyes, and respiratory tract.
|
| References | |
| Additional Infomation |
This compound (also known as 14f) is a member of the 1,3-diphenylpyrazine class of Skp2 inhibitors. It is a research-grade chemical only and is not an FDA-approved drug. It is used as a chemical probe to study the role of the Skp2-SCF E3 ubiquitin ligase complex in cell cycle regulation and tumorigenesis. It was first described in the Journal of Medicinal Chemistry in 2023.
|
| Molecular Formula |
C27H32N4O
|
|---|---|
| Molecular Weight |
428.569186210632
|
| Exact Mass |
428.257
|
| CAS # |
2760612-77-7
|
| PubChem CID |
162718217
|
| Appearance |
White to off-white solid powder
|
| LogP |
5
|
| Hydrogen Bond Donor Count |
1
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
6
|
| Heavy Atom Count |
32
|
| Complexity |
583
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
CC(C)(C)C(=O)NCC1CCN(CC1)C2=CN=C(C(=N2)C3=CC=CC=C3)C4=CC=CC=C4
|
| InChi Key |
GCCXPXBVXWVREI-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/C27H32N4O/c1-27(2,3)26(32)29-18-20-14-16-31(17-15-20)23-19-28-24(21-10-6-4-7-11-21)25(30-23)22-12-8-5-9-13-22/h4-13,19-20H,14-18H2,1-3H3,(H,29,32)
|
| Chemical Name |
N-[[1-(5,6-diphenylpyrazin-2-yl)piperidin-4-yl]methyl]-2,2-dimethylpropanamide
|
| 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 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)
|
| Solubility (In Vitro) |
DMSO: 12 mg/mL (28.00 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 | 2.3333 mL | 11.6667 mL | 23.3334 mL | |
| 5 mM | 0.4667 mL | 2.3333 mL | 4.6667 mL | |
| 10 mM | 0.2333 mL | 1.1667 mL | 2.3333 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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