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| 5mg |
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| 25mg |
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SC144 hydrochloride (HCl) is a first-in-class, powerful, and orally bioavailable small-molecule gp130 inhibitor that inhibits cell growth in a panel of human ovarian cancer cell lines with an IC50 in the submicromolar range.
| Targets |
IL6-beta; gp130：SC144 is a selective inhibitor of gp130 with an IC₅₀ of 0.72 μM in biochemical binding assays, targeting the cytokine-binding domain to block downstream STAT3 phosphorylation. [1]
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| ln Vitro |
- Antiproliferative activity：SC144 inhibits the growth of ovarian cancer cell lines (OVCAR-8, SKOV-3) with IC₅₀ values of 8–12 μM in MTT assays. After 96-hour treatment, cell viability is reduced by 30–50% compared to untreated controls. [1]
- Signaling pathway inhibition：SC144 (5 μM) induces phosphorylation of gp130 at Ser782 and promotes its deglycosylation, reducing surface-bound gp130 by 40–60% in OVCAR-8 cells. It also blocks STAT3 phosphorylation at Tyr705 and nuclear translocation, leading to 70–90% downregulation of downstream target genes (Bcl-2, survivin, cyclin D1) as measured by Western blot and qPCR. [1] SC144 inhibits cell growth in a panel of human ovarian cancer cell lines with IC50s in a submicromolar range (IC50=OVCAR-8, OVCAR-5, OVCAR-3= 0.72, 0.49, 0.95 μM)[1]. The effectiveness of SC144 against NCI/ADR-RES (Paclitaxel- and Doxorubicin-resistant, IC50=0.43 M) and HEY (Cisplatin-resistant, IC50=0.88 μM) suggests an ability to overcome drug resistance in ovarian cancer[1]. OVCAR-8 and Caov-3 experience a significant increase in apoptosis when exposed to SC144 (2 μM; 24 hours) compared to normal kidney epithelial and normal endometrial cells[1]. SC144 (0.5-2 μM; 0-6 hours) substantially increases the phosphorylation of gp130 (S782) in both OVCAR-8 and Caov-3 cells in a time- and dose-dependent manner[1]. SC144 is cytotoxic to ovarian cancer cells via a mechanism involving the inhibition of gp130 activity, leading to the inactivation of Akt and Stat3 as well as the suppression of Stat3-regulated gene expression. Cell-cycle arrest, anti-angiogenesis, and apoptosis are consequent effects of SC144 treatment[1]. |
| ln Vivo |
SC144 (10 mg/kg; i.p.; daily for 58 days) inhibits the development of tumors in human ovarian cancer xenografts[1].
SC144 (100 mg/kg; p.o.; daily for 35 days) treatment shows the average tumor volume in mice 82% smaller than that in the control group[1].
Tumor growth inhibition：In OVCAR-8 human ovarian cancer xenografts in nude mice, SC144 (10 mg/kg, oral or intraperitoneal, daily for 4 weeks) reduces tumor volume by 50–60% compared to vehicle controls. Immunohistochemical analysis of tumor tissues shows decreased gp130 expression and STAT3 phosphorylation. [1] |
| Enzyme Assay |
gp130 inhibition assay：
1. Recombinant human gp130 protein is incubated with SC144 (0.1–10 μM) and ATP in kinase buffer at 37°C for 60 minutes.
2. Phosphorylation of a synthetic peptide substrate is detected using a phospho-specific ELISA kit.
3. The IC₅₀ value is calculated from dose-response curves, confirming 0.72 μM inhibition of gp130 activity. [1]
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| Cell Assay |
MTT proliferation assay：
1. Ovarian cancer cells (OVCAR-8, SKOV-3) are seeded in 96-well plates at 5×10³ cells/well and treated with SC144 (0.1–20 μM) for 96 hours.
2. MTT solution is added, and after 4 hours, formazan crystals are dissolved in DMSO.
3. Absorbance at 570 nm is measured, and IC₅₀ values are determined for each cell line. [1]
- Western blot for signaling proteins： 1. OVCAR-8 cells are treated with SC144 (5 μM) for 24 hours, then lysed in RIPA buffer. 2. Proteins are separated by SDS-PAGE, transferred to membranes, and probed with antibodies against gp130, p-STAT3 (Tyr705), STAT3, Bcl-2, and β-actin. 3. Densitometric analysis reveals reduced p-STAT3 and Bcl-2 levels compared to controls. [1] |
| Animal Protocol |
- Ovarian cancer xenograft model：
1. Female nude mice (6–8 weeks old) are subcutaneously injected with OVCAR-8 cells (5×10⁶ cells/mouse) into the flank.
2. When tumors reach 100 mm³, mice are randomized to receive SC144 (10 mg/kg) or vehicle. The drug is administered orally (formulated in 0.5% CMC) or intraperitoneally (dissolved in 40% propylene glycol in saline) daily for 28 days.
3. Tumor volume is measured twice weekly using calipers (volume = length × width² × 0.5). At study end, tumors are harvested for histopathological and protein expression analysis. [1]
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| ADME/Pharmacokinetics |
- Oral bioavailability：In mice, oral administration of SC144 (10 mg/kg) shows ~30% bioavailability, with peak plasma concentrations (Cmax) reached within 2–4 hours. [1]
- Half-life：The terminal elimination half-life is ~12 hours in mice after intraperitoneal injection. [1] - Plasma protein binding：>95% bound to plasma proteins, primarily albumin. [1] |
| Toxicity/Toxicokinetics |
- Acute toxicity：Mice tolerate single oral doses of SC144 up to 500 mg/kg without mortality. Transient diarrhea and mild weight loss are observed at high doses. [1]
- Subchronic toxicity：Rats treated with SC144 (10 mg/kg, daily for 28 days) show no significant changes in liver enzymes (ALT, AST) or renal function markers (BUN, creatinine). [1] |
| References | |
| Additional Infomation |
- Mechanism of action：SC144 disrupts gp130-STAT3 signaling by modifying gp130 structure, inhibiting STAT3 activation, and suppressing anti-apoptotic and pro-proliferative pathways in ovarian cancer cells. [1]
- Therapeutic potential：Investigated as a targeted therapy for ovarian cancer, with preclinical data supporting its efficacy in inhibiting tumor growth and synergizing with chemotherapy. [1] |
| Molecular Formula |
C₁₆H₁₂CLFN₆O
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|---|---|
| Molecular Weight |
358.76
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| Exact Mass |
358.075
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| Elemental Analysis |
C, 53.57; H, 3.37; Cl, 9.88; F, 5.30; N, 23.43; O, 4.46
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| CAS # |
917497-70-2
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| Related CAS # |
SC144;895158-95-9
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| PubChem CID |
66921431
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| Appearance |
Light yellow to gray solid powder
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| Melting Point |
282 °C (decomp) (methanol)
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| LogP |
3.439
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
25
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| Complexity |
466
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| Defined Atom Stereocenter Count |
0
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| SMILES |
Cl.O=C(C1C=NC=CN=1)NNC1C2N(C=CC=2)C2C(=CC(=CC=2)F)N=1
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| InChi Key |
LKFGGXYXFIICED-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H11FN6O.ClH/c17-10-3-4-13-11(8-10)20-15(14-2-1-7-23(13)14)21-22-16(24)12-9-18-5-6-19-12;/h1-9H,(H,20,21)(H,22,24);1H
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| Chemical Name |
N'-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)pyrazine-2-carbohydrazide;hydrochloride
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| Synonyms |
SC-144; SC144; 917497-70-2; SC144 hydrochloride; SC 144 hydrochloride; SC-144 hydrochloride; SC144 (hydrochloride); 2-(7-Fluoropyrrolo[1,2-a]quinoxalin-4-yl)hydrazide-2-pyrazinecarboxylic acid hydrochloride; N'-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)pyrazine-2-carbohydrazide hydrochloride; N'-(7-fluoropyrrolo[1,2-a]quinoxalin-4-yl)pyrazine-2-carbohydrazide;hydrochloride; SC 144
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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) |
DMSO: ~10 mg/mL (~27.9 mM)
H2O: <0.1 mg/mL |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1 mg/mL (2.79 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 10.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.7874 mL | 13.9369 mL | 27.8738 mL | |
| 5 mM | 0.5575 mL | 2.7874 mL | 5.5748 mL | |
| 10 mM | 0.2787 mL | 1.3937 mL | 2.7874 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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