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| 10mg |
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Purity: ≥98%
SC-514 (SC 514; SC514) is a novel, potent, orally bioactive, selective and reversible, and ATP-competitive IKK-2 inhibitor with potential anti-inflammatory activity. With an IC50 of 3–12 μM, it only inhibits IKK2 and does not affect other IKK isoforms. The treatment of osteoclastogenesis may be possible with SC-514.
| Targets |
IKK-2 (IC50 = 11.2 μM); CDK2/A (IC50 = 61 μM); AUR2 (IC50 = 71 μM); PRAK (IC50 = 75 μM); MSK (IC50 = 123 μM)
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| ln Vitro |
SC-514 inhibits the native IKK complex or recombinant human IKK-1/IKK-2 heterodimer and IKK-2 homodimer similarly. In IL-1β-induced synovial fibroblasts (RASFs) derived from rheumatoid arthritis, SC-514 inhibits transcription of NF-κB-dependent IL-6, IL-8, and COX-2 genes with IC50 values of 20, 20, and 8 μM. 100 μM In RASFs treated with IL-1, SC-514 decreases the level of p65 translocation into the nucleus, inhibits the phosphorylation and degradation of IκBα , and blocks the phosphorylation and degradation of IκBα. Activation and phosphorylation of the IKK complex are not inhibited by SC-514. IB phosphorylation and degradation are partially blocked by SC-514, but not entirely. P65 import into the nucleus in SC-514 treatment cells is slightly slowed and reduced, and p65 export from the nucleus is accelerated. Either I-B or p65 are equally inhibited by SC-514's ability to phosphorylate them.[1]
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| ln Vivo |
In an acute model of inflammation that involves LPS-induced serum TNF-α production, SC-514 is effective. In vivo, SC-514 (50 mg/kg, i.p.) reduces TTNF-α-production by 70%. [1]
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| Enzyme Assay |
Using a NEMO antibody (3-10 μg) and protein A-agarose beads, IKK complexes are immunoprecipitated from IL-1β-treated RASF cell lysates (0.5-2 mg). Antibody complexes are centrifuged and then washed twice in kinase buffer (25 mM HEPES, pH 7.6, 2 mM MgCl2, 2 mM MnCl2, 10 mM NaF, 5 mM DTT, and 1 mM phenylmethylsulfonyl fluoride) before being washed three times in cold whole-cell lysis buffer. In a reaction with 10 mM biotinylated IB peptide as substrate and 1 mM [γ-33P]ATP (2500 Ci/mmol), 100–200 g of immunoprecipitated IKK are used to measure the kinase activity. The kinase activity of 100–200 μg of immunoprecipitated IKK is assessed in a reaction with 10 μM biotinylated IB peptide as substrate and 1 μM [γ-33P]ATP (2500 Ci/mmol). A SAM 96 biotin capture plate is then filled with 25 μL of the reaction mixture following a 30-minute incubation at room temperature. Following each wash step, the plate was allowed to air dry before each well received 25 μL of scintillation fluid. A Top-Count NXT[1] is used to measure [γ-33P]ATP incorporation.
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| Cell Assay |
Melanoma cell lines (1×104) are plated in 60 mm dishes and either left untreated or pretreated with SC-514 (50 µM) and/or Fotemustine for the crystal violet staining assay. Following formalin fixation and crystal violet staining, cells are prepared. The optical density at 595 nm (OD595) of solubilized crystal violet from formalin-fixed cells is used to calculate the number of cells. The MTT reduction assay is another method for determining cytotoxicity.
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| Animal Protocol |
Rats: Adult male Wistar rats are given either SC-514 or vehicle (2% Me2SO in saline) by intraperitoneal injection (10 and 50 mg/kg) or oral gavage (50 mg/kg) after an overnight fast. One mg/kg of LPS (Escherichia coli) in saline is given intraperitoneally two hours after compound treatment. Ninety minutes later, the animals are bled, and serum TNF levels are measured using a rat-specific TNFα ELISA.
Mice: Six-week-old male nu/nu BALB/c mice are kept in separate ventilated cages. Reconstituted A375 or G361 (5×106) cells are inoculated subcutaneously into the backs of naked mice, where they are allowed to grow for 7 days. After that, mice are divided into 4 groups at random (n=6) and given intraperitoneal injections of a 200 µL solution containing 30% PEG/5% Tween-80 as the vehicle control, 25 mg/kg SC-514, or 25 mg/kg Fotemustine, once daily for 13–15 days. Every three days, the tumor volume and body weight are measured. Using a caliper, tumor volumes are measured and calculated. Mice are killed at the conclusion of the experiment, and tumor xenografts are gathered. For a Western blot analysis, tumor tissues are kept at -80°C. |
| References |
| Molecular Formula |
C9H8N2OS2
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| Molecular Weight |
224.3
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| Exact Mass |
224.296
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| Elemental Analysis |
C, 48.19; H, 3.60; N, 12.49; O, 7.13; S, 28.59
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| CAS # |
354812-17-2
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| Related CAS # |
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| Appearance |
Solid powder
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| SMILES |
C1=CSC=C1C2=CC(=C(S2)C(=O)N)N
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| InChi Key |
BMUACLADCKCNKZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C9H8N2OS2/c10-6-3-7(5-1-2-13-4-5)14-8(6)9(11)12/h1-4H,10H2,(H2,11,12)
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| Chemical Name |
3-amino-5-thiophen-3-ylthiophene-2-carboxamide
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| Synonyms |
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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 |
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| 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) |
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| Solubility (In Vivo) |
2% DMSO+30% PEG 300+2% Tween 80+ddH2O: 4mg/mL (Please use freshly prepared in vivo formulations for optimal results.)
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| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.4583 mL | 22.2916 mL | 44.5831 mL | |
| 5 mM | 0.8917 mL | 4.4583 mL | 8.9166 mL | |
| 10 mM | 0.4458 mL | 2.2292 mL | 4.4583 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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