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LB-100

CAS No. : 1632032-53-1

MCE 國際站：LB-100

產(chǎn)品活性：LB-100 是一種蛋白磷酸酶 2A (protein phosphatase 2A) 抑制劑，在 BxPc-3 和 Panc-1 細胞中，IC₅₀ 值分別為 0.85 μM 和 3.87 μM。

研究領(lǐng)域：Metabolic Enzyme/Protease

作用靶點：Phosphatase

In Vitro: LB-100 inhibits the cell growth with IC₅₀ of 2.3 μM (in BxPc-3) or 1.7 μM (in Panc-1 cell). In BxPc-3, Panc-1, and SW1990 cells, LB-100 reduces the PP2A activity by 30-50%. LB-100 increases concentration of doxorubicin within cells (2.5 fold to control) and sensitizes tumor cells to the cytotoxicity of doxorubicin. LB-100 increaseds VEGF secretion, and thus enhances HIF-1α-VEGF mediated angiogenesis. LB-100 alters VE-cadherin integrity between endothelial cells. Pretreatment of LB-100 results in a nearly 40% increase in dye passing through the HUVECs monolayer. LB-100 induces higher paracellular permeability of vascular endothelial cells potentially accounting for LB-100 increasing the concentration of doxorubicin in tumor cells. LB-100 downregulates Bcl-2 expression and enhances sorafenib-induced apoptosis in HCC cells.

In Vivo: LB-100 (2 mg/kg, i.p.) decreases in a time-dependent manner the activity of PP2A in xenografts and livers in nude mice. LB-100 does not alter the expression of the three PP2A subunits (PP2A_A, PP2A_B, and PP2A_C) in cell lines, xenografts, or livers, as confirmed by immunoblotting. The combination of doxorubicin (1.5 kg/mL, every other day) and LB-100 (2 mg/kg, every other day) significantly slows the growth of tumors with reduction of tumor volume in two animals with no effects on tumor growth in animals treated with single agents.

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