CAS Number354812-17-2
Synonyms4-Amino-2,3'-bithiophene-5-carboxamide; 4-Amino-[2,3"]bithiophenyl-5-carboxylic acid amide; SC-514; GK 01140
Molecular FormulaC9H8N2OS2
Molecular Weight224.303
Density1.5±0.1 g/cm3
Boiling Point399.2±42.0 °C at 760 mmHg
Melting Point209-211°C
Appearancewhite to light brown
| Chemical & Physical Properties | |
|---|---|
| CAS Number | 354812-17-2 |
| Catalog No. | 2A-1169192 |
| Chinese Name | 4-氨基-[2,3']联噻吩-5-甲酰胺 |
| Synonyms | 4-Amino-2,3'-bithiophene-5-carboxamide; 4-Amino-[2,3"]bithiophenyl-5-carboxylic acid amide; SC-514; GK 01140 |
| Molecular Formula | C9H8N2OS2 |
| Molecular Weight | 224.303 |
| Density | 1.5±0.1 g/cm3 |
| Boiling Point | 399.2±42.0 °C at 760 mmHg |
| Melting Point | 209-211°C |
| Appearance | white to light brown |
| Water Solubility | DMSO: soluble10mg/mL, clear |
| Storage Condition | Store at +4°C |
| Application | SC-514 is a selective IKK-2 inhibitor (IC50=11.2±4.7 μM) and does not inhibit other IKK isoforms or other serine-threonine and tyrosine kinases. |
| PubChem ID | 3265879 |
| SMILES | NC(=O)c1sc(-c2ccsc2)cc1N |
| InChI | 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) |
| InChI Key | BMUACLADCKCNKZ-UHFFFAOYSA-N |
| Bioactivity | SC-514 is a selective IKK-2 inhibitor (IC50=11.2±4.7 μM), which does not inhibit other IKK isoforms or other serine-threonine and tyrosine kinases. Related Catalog Signaling Pathways >> NF-κB >> IKK Research Areas >> Cancer Target IKK-2:11.2 μM (IC50) CDK2/A:61 μM (IC50) AUR2:71 μM (IC50) PRAK:75 μM (IC50) MSK:123 μM (IC50) In Vitro SC-514 inhibits the native IKK complex or recombinant human IKK-1/IKK-2 heterodimer with IC50s of 6.1±2.2 μM and 2.7±0.7 μM, respectively. IKK-2 inhibition by SC-514 is selective, reversible, and competitive with ATP. SC-514 inhibits transcription of NF-κB-dependent genes in IL-1β-induced rheumatoid arthritis-derived synovial fibroblasts in a dose-dependent manner. SC-514 inhibits all forms of recombinant human IKK-2 including rhIKK-2 homodimer, rhIKK-1/rhIKK-2 heterodimer, as well as the constitutively active form of rhIKK-2 with comparable IC50 values in the 3-12 μM range[1]. To evaluate whether the reactive oxygen species (ROS)-inducing IKKβ inhibitor increases the sensitivity of melanoma cells to nitrosourea. The responses of melanoma cells are first assessed to SC-514/Fotemustine co-treatment. Melanoma cell lines are treated with 50 µM of SC-514 and Fotemustine alone and in combination for 48 h and growth inhibition is assessed. Co-treatment with SC-514 significantly enhances Fotemustine-induced cytotoxicity in all melanoma cell lines tested[2]. In Vivo SC-514 is efficacious in an acute model of inflammation, namely LPS-induced serum TNFα production in the rat. SC-514 shows a dose-dependent inhibition of TNFα production, validating IKK-2 as a potential anti-inflammatory drug target in vivo[1]. To obtain in vivo evidence for the implication of SC-514 in the response of cancer cells to Fotemustine, the xenograft mouse model of melanoma is used. Nude mice engrafted with A375 or G361 tumors are treated with vehicle control and 25 mg/kg SC-514 and/or 25 mg/kg Fotemustine daily for 13-15 consecutive days and the tumor behavior is monitored. Fotemustine treatment with SC-514 shows a clear combined effect and reduces the size of tumors in mice[2]. Kinase Assay IKK complexes are immunoprecipitated from IL-1β-treated RASF cell lysates (0.5-2 mg) using a NEMO antibody (3-10 μg) followed by the addition of protein A-agarose beads. Antibody complexes are pelleted by centrifugation and washed 3 times with 1 mL of cold whole-cell lysis buffer followed by 2 washes 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). 100-200 μg of immunoprecipitated IKK is analyzed for kinase activity in a reaction containing 10 μM biotinylated IκBα peptide as substrate and 1 μM [γ-33P]ATP (2500 Ci/mmol). After incubation at room temperature for 30 min, 25 μL of the reaction mixture is withdrawn and added to a SAM 96 biotin capture plate. After successive wash steps the plate was allowed to air-dry, and 25 μL of scintillation fluid is added to each well. Incorporation of [γ-33P]ATP is measured using a Top-Count NXT[1]. Cell Assay For crystal violet staining assay, melanoma cell lines (1×104) are seeded in 60 mm dishes, and then untreated or pretreated with SC-514 (50 µM) and/or Fotemustine. Then, cells are formalin-fixed and stained with crystal violet. Cell numbers are measured as the optical density at 595 nm (OD595) of solubilized crystal violet from formalin-fixed cells. Cytotoxicity are also determined by the MTT reduction assay[2]. Animal Admin Rats[1] SC-514 or vehicle (2% Me2SO in saline) is administered either by oral gavage (50 mg/kg) or intraperitoneally (10 and 50 mg/kg) to adult male Wistar rats that have been deprived of food overnight. Two hours after compound treatment, 1 mg/kg LPS (Escherichia coli) in saline is administered intraperitoneally 90 min after LPS administration; the animals are bled and serum TNFα levels analyzed by a rat-specific TNFα ELISA. Mice[2] Male nu/nu BALB/c mice (6 weeks old) are maintained in individual ventilated cages. A375 or G361 (5×106) cells are resuspended in 0.1 mL PBS and inoculated subcutaneously into the backs of nude mice and allowed to grow for 7 days. After that, mice are randomly assigned to 4 groups (n=6 for each group) and treated by intraperitoneal injection with 200 µL 30% PEG/5% Tween-80 solution as the vehicle control and 25 mg/kg SC-514 and/or 25 mg/kg Fotemustine daily for 13-15 consecutive days. Body weight and tumor volume are measured every 3 days. Tumor volumes are determined by a caliper and calculated. At the end of the experiment, mice are sacrificed and tumor xenografts are collected. Tumor tissues are stored at -80°C for Western blot analysis. References [1]. Kishore N, et al. A selective IKK-2 inhibitor blocks NF-kappa B-dependent gene expression in interleukin-1 beta-stimulated synovial fibroblasts. J Biol Chem. 2003 Aug 29;278(35):32861-71. [2]. Tse AK, et al. Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKKβ inhibition. Redox Biol. 2017 Apr;11:562-576. Chemical & Physical Properties Density 1.5±0.1 g/cm3 Boiling Point 399.2±42.0 °C at 760 mmHg Melting Point 209-211°C Molecular Formula C9H8N2OS2 Molecular Weight 224.303 Flash Point 195.2±27.9 °C Exact Mass 224.007797 PSA 125.59000 LogP 1.52 Appearance of Characters white to light brown Vapour Pressure 0.0±0.9 mmHg at 25°C Index of Refraction 1.715 InChIKey BMUACLADCKCNKZ-UHFFFAOYSA-N SMILES NC(=O)c1sc(-c2ccsc2)cc1N Storage condition Store at +4°C Water Solubility DMSO: soluble10mg/mL, clear |
| Use of | Properties Name 3-amino-5-thiophen-3-ylthiophene-2-carboxamide Synonym More Synonyms SC-514 Biological Activity Related Catalog Signaling Pathways >> NF-κB >> IKK Research Areas >> Cancer IKK-2:11.2 μM (IC50) AUR2:71 μM (IC50) PRAK:75 μM (IC50) MSK:123 μM (IC50) References [1]. Kishore N, et al. A selective IKK-2 inhibitor blocks NF-kappa B-dependent gene expression in interleukin-1 beta-stimulated synovial fibroblasts. J Biol Chem. 2003 Aug 29;278(35):32861-71. [2]. Tse AK, et al. Sensitization of melanoma cells to alkylating agent-induced DNA damage and cell death via orchestrating oxidative stress and IKKβ inhibition. Redox Biol. 2017 Apr;11:562-576. Chemical & Physical Properties Molecular Formula C9H8N2OS2 Exact Mass 224.007797 PSA 125.59000 Appearance of Characters white to light brown Index of Refraction 1.715 InChIKey BMUACLADCKCNKZ-UHFFFAOYSA-N |
| Transport Info | Product name: SC-514 |
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