SC-43

SKU: orb1220021

Description

SC-43 is a potent and orally active agonist of SHP-1 (PTPN6). SC-43 inhibits the phosphorylation of STAT3 and induces cell apoptosis, and with anti-fibrotic and anticancer effects.SC-43, a sorafenib derivative.SC-43-induced apoptosis in cholangiocarcinoma (CCA) via a novel mechanism. Three CCA cell lines (HuCCT-1, KKU-100 and CGCCA) were treated with SC-43 to determine their sensitivity to SC-43-induced cell death and apoptosis. SC-43 activated SH2 domain-containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream cyclin B1 and Cdc2 downregulation, which induced G2-M arrest and apoptotic cell death. Importantly, SC-43 augmented SHP-1 activity by direct binding to N-SH2 and relief of its autoinhibition. Deletion of the N-SH2 domain (dN1) or point mutation (D61A) of SHP-1 counteracted the effect of SC-43-induced SHP-1 phosphatase activation and antiproliferation ability in CCA cells. In vivo assay revealed that SC-43 exhibited xenograft tumor growth inhibition, p-STAT3 reduction and SHP-1 activity elevation.

Key Properties

• CAS Number: 1400989-25-4
• MW: 431.8
• Purity: >98% (HPLC)
• Formula: C₂₁H₁₃ClF₃N₃O₂?
• SMILES: FC(F)(F)c1cc(NC(=O)Nc2cccc(Oc3ccc(cc3)C#N)c2)ccc1Cl
• Target: Phosphatase
• Solubility: In Vitro: DMSO : 250 mg/mL (578.97 mM)

Bioactivity

• In Vivo:
  Animal model: Male NCr athymic nude mice (5-7 weeks of age) injected with HuCCT-1 cells. Dosage: 10 mg/kg or 30 mg/kg. Administration: Oral gavage; daily; for 23 days. Result: Exhibited xenograft tumor growth inhibition, p-STAT3 reduction and SHP-1 activity elevation.
• In Vitro:
  Cell Viability Assay Cell line: HuCCT-1, KKU-100, and CGCCA cells. Concentration: 0 μM, 0.25 μM, 0.5 μM, 0.75 μM, 1 μM, 2.5 μM, 5 μM, 10 μM Incubation time: 24 hours, 48 hours, 72 hours. Result: Revealed the anti-proliferative effects in CCA cell lines in a dose-dependent manner after treating 24, 48 and 72 hours respectively. Cell Cycle Analysis Cell line: HuCCT-1, KKU-100, and CGCCA cells. Concentration: 0 μM, 1 μM, 2.5 μM, 5 μM, 10 μM Incubation time: 24 hours. Result: Showed increased sub-G1 cells and G2-M arrest. Western blot analysis. Cell line: HuCCT-1, KKU-100, and CGCCA cells. Concentration: 0 μM, 1 μM, 2.5 μM, 5 μM, 10 μM Incubation time: 24 hours. Result: Demonstrated significant increase in cleaved caspase-3 and PARP level.

Storage & Handling

• Storage: Storage temperature: -20°C. Stability: ≥ 2 years
• Expiration Date: 12 months from date of receipt.
• Disclaimer: For research use only

Quick Database Links

Gene Symbol

Phosphatase