SC 144
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.
- 1. Ruaa Al-Qazazi, Patricia D A Lima, et al. "Macrophage-NLRP3 Activation Promotes Right Ventricle Failure in Pulmonary Arterial Hypertension." Am J Respir Crit Care Med. 2022 Sep 1;206(5):608-624. PMID: 35699679
- 2. Marie R.Mooney. "Precision Medicine Approaches to Integrating Genomics with Cancer Therapy: Applications in Glioblastoma and Lymphoma." ProQuest LLC.2016
| Physical Appearance | A solid |
| Storage | Store at -20°C |
| M.Wt | 322.3 |
| Cas No. | 895158-95-9 |
| Formula | C16H11FN6O |
| Solubility | insoluble in EtOH; insoluble in H2O; ≥16.1 mg/mL in DMSO |
| Chemical Name | N'-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)pyrazine-2-carbohydrazide |
| SDF | Download SDF |
| Canonical SMILES | FC1=CC(N=C(NNC(C2=NC=CN=C2)=O)C3=CC=CN34)=C4C=C1 |
| Shipping Condition | Small Molecules with Blue Ice, Modified Nucleotides with Dry Ice. |
| General tips | We do not recommend long-term storage for the solution, please use it up soon. |
| Kinase experiment [1]: | |
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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]: | |
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Cell lines |
OVCAR-8, OVCAR-5, OVCAR-3, Caov-3, SKOV-3, HEY and NCI/ADR-RES |
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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. |
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Reaction Conditions |
~ 10 μM; 96 hrs |
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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]: | |
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Animal models |
OVCAR-8 xenograft mouse model |
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Dosage form |
10 mg/kg; i.p. or p.o.; q.d. |
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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. |
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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. |
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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. |
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| Description | 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 | |||||
| Targets | gp130 | |||||
| IC50 | ||||||
Quality Control & MSDS
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Chemical structure
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