SC 144 |
| Catalog No.GC15714 |
Gp130 inhibitor
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 895158-95-9
Sample solution is provided at 25 µL, 10mM.
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SC144 is an inhibitor of gp130 with IC50 values of 0.43 μmol/L and 0.88 μmol/L in NCI/ADR-RES and HEY cell lines, respectively [1].
SC144 is a first-in-class small-molecule gp130 inhibitor with oral activity in ovarian cancer. It can substantially increase the phosphorylation of gp130 (S782) in both OVCAR-8 and Caov-3 cells in a time- and dose-dependent manner. The increase phosphorylation then suppresses Stat3 signaling pathway since the constitutive Stat3 activation is maintained by extracellular gp130 ligands, Besides that, SC144 also causes substantial cell apoptosis in these cells. [1].
Apart from the effect on gp130, it has been reported that SC144 can directly bind and stabilize IL-24 in cancer cells. Additionally, SC144 has shown to have effects on cell cycle perturbation and apoptosis induction [2].
SC144 may also have other cellular protein targets, resulting in multiple potential molecular mechanisms. SC144’s anticancer potency may be a sum of these effects [2].
References:
[1] Shili Xu, Fedora Grande, Antonio Garofalo, et al. Discovery of a Novel Orally Active Small-Molecule gp130 Inhibitor for the Treatment of Ovarian Cancer. Molecular Cancer Therapeutics. 2013 (12): 937-949.
[2] Shili Xu, Takashi Oshima, Toshio Imada, Munetaka Masuda, Bikash Debnath, Fedora Grande, Antonio Garofalo, Nouri Neamati. Stabilization of MDA-7/IL-24 for colon cancer therapy. Cancer Letters. 2013 Feb(335):421-430.
| Kinase experiment [1]: | |
|
Binding assays |
OVCAR-8 cells were lysed using M-PER supplemented with protease and phosphatase inhibitors. The supernatant of cell lysate containing 4 to 6 μg/μL total proteins was incubated with SC144 at indicated concentrations (0, 1, 10, 100, 1000 μmol/L) at room temperature for 1 hr, followed by proteolysis with 1 μg pronase to every 9,600 μg of lysate for 30 mins at room temperature. Final concentration of DMSO was 1% in all samples. To stop proteolysis, 5 × SDS sample loading buffer [Tris-HCl 0.25 mol/L, pH 6.8, SDS 10%, glycerol 50%, bromophenol blue 0.5%, dithiothreitol (DTT) 100 mmol/L] was added to each sample at a 1:4 ratio, mixed well, and boiled at 100℃ for 5 mins. Samples were analyzed by Western blotting. |
| Cell experiment [1]: | |
|
Cell lines |
OVCAR-8, OVCAR-5, OVCAR-3, Caov-3, SKOV-3, HEY and NCI/ADR-RES |
|
Preparation method |
The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
|
Reaction Conditions |
~ 10 μM; 96 hrs |
|
Applications |
SC144 treatment in vitro induced gp130 phosphorylation and deglycosylation, resulting in the downregulation of surface-bound gp130 and the abrogation of gp130-associated Stat3 activation. In addition, SC144 selectively inhibited the downstream signaling activation induced by gp130 substrates, including IL-6 and LIF. In OVCAR-8 cells, protein expression regulated by the gp130/Stat3 axis was also down-regulated after SC144 treatment, including Bcl-2, Bcl-XL, survivin, cyclin D1, MMP-7, gp130 and Ape1/Rel-1. |
| Animal experiment [1]: | |
|
Animal models |
OVCAR-8 xenograft mouse model |
|
Dosage form |
10 mg/kg; i.p. or p.o.; q.d. |
|
Applications |
In a mouse xenograft model of human ovarian cancer, SC144 significantly inhibited tumor growth. After the exposure to SC144 for 2 months, gp130, Bcl-2, Bcl-XL, MMP-7 and Ape1/Ref-1 protein levels were substantially decreased in the tumor site in the treatment group compared with the control group. |
|
Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
|
References: [1]. Shili Xu, Fedora Grande, Antonio Garofalo, et al. Discovery of a Novel Orally Active Small-Molecule gp130 Inhibitor for the Treatment of Ovarian Cancer. Molecular Cancer Therapeutics. 2013 (12): 937-949. | |
| Cas No. | 895158-95-9 | SDF | |
| Canonical SMILES | FC1=CC(N=C(NNC(C2=NC=CN=C2)=O)C3=CC=CN34)=C4C=C1 | ||
| Formula | C16H11FN6O | M.Wt | 322.3 |
| Solubility | ≥ 16.1mg/mL in DMSO | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
||
| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.1027 mL | 15.5135 mL | 31.027 mL |
| 5 mM | 0.6205 mL | 3.1027 mL | 6.2054 mL |
| 10 mM | 0.3103 mL | 1.5513 mL | 3.1027 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid 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 master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 26 reference(s) in Google Scholar.)
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