SC-43

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

SC-43 是一种有效的口服活性 SHP-1 (PTPN6) 激动剂。 SC-43抑制STAT3磷酸化并诱导细胞凋亡，并具有抗纤维化和抗癌作用。SC-43，索拉非尼衍生物。

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.

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.

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.

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Metabolic Enzyme/Protease

Phosphatase

SHP-1|STAT3|apoptosis

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1400989-25-4

431.8

C21H13ClF3N3O2?

>98% (HPLC)

In Vitro:?DMSO : 250 mg/mL (578.97 mM)

FC(F)(F)c1cc(NC(=O)Nc2cccc(Oc3ccc(cc3)C#N)c2)ccc1Cl

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(-20℃)

With Ice Pack

≥ 2 years