SC-43 (10-30 mg/kg; oral gavage; daily; for 23 days; male NCr athymic nude mice) treatment exhibits xenograft tumor growth inhibition, p-STAT3 reduction and SHP-1 activity elevation[1]. Animal Model: Male NCr athymic nude mice (5-7 weeks of age) injected with HuCCT-1 cells[1] 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
SC-43 (0-10 μM; 24-72 hours; HuCCT-1, KKU-100, and CGCCA cells) treatment reveals the anti-proliferative effects in cholangiocarcinoma (CCA) cell lines in a dose-dependent manner after treating 24, 48 and 72 hours respectively[1]. SC-43 (0-10 μM; 24 hours; HuCCT-1, KKU-100, and CGCCA cells) treatment shows increased sub-G1 cells and G2-M arrest, indicating SC-43 induced differential apoptotic effects in these cell lines[1]. SC-43 (0-10 μM; 24 hours; HuCCT-1, KKU-100, and CGCCA cells) treatment demonstrates significant increase in cleaved caspase-3 and PARP level[1]. SC-43 activates SH2 domain-containing phosphatase 1 (SHP-1) activity, leading to p-STAT3 and downstream cyclin B1 and Cdc2 downregulation. SC-43 augments SHP-1 activity by direct binding to N-SH2 and relief of its autoinhibition[1]. Cell Viability Assay[1] 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[1] 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[1] 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.
Kinase Assay
Cell Assay
Animal Administration
References
[1]. Ming-Hung Hu, et al. Targeting SHP-1-STAT3 signaling: A promising therapeutic approach for the treatment of cholangiocarcinoma. Oncotarget. 2017 May 10;8(39):65077-65089.
[2]. Tung-Hung Su, et al. Src-homology protein tyrosine phosphatase-1 agonist, SC-43, reduces liver fibrosis. Sci Rep. 2017 May 11;7(1):1728.
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