QS11

QS11 is a GTPase activating protein of ADP-ribosylation factor 1 (ARFGAP1) inhibitor.

Signaling Pathways >> Others >> Others

Research Areas >> Cancer

QS11 binds and inhibits the GTPase activating protein of ADP-ribosylation factor 1 (ARFGAP1), suggesting that QS11 modulates Wnt/β-catenin signaling through an effect on protein trafficking. QS11 (2.5 μM) activates the Super(8X)TOPFlash reporter 200-fold in the presence of Wnt-3a CM, whereas Wnt-3a treatment alone increases reporter activity 40-fold. QS11 increases reporter activity only 2-fold in the absence of Wnt-3a. QS11 shows potent activity (EC50=0.5 μM) with little cytotoxicity toward HEK293 and human primary fibroblast cells. QS11 effectively reduces in vitro migration of metastatic human breast cancer cells[1].

ARF-GTP levels are measured by using the GGA binding assay. NIH 3T3 cells are treated with QS11 or QS11-NC at the indicated concentrations for 36 h. Cells are lysed in ARF assay lysis buffer [50 mM Tris·HCl (pH 7.5), 100 mM NaCl, 2 mM MgCl2, 0.1% SDS, 0.5% sodium deoxycholate, 1% Triton X-100, 10% glycerol, and protease inhibitors]. GTP-bound ARF is assayed by its binding to a GST fusion protein, which contains the VHS domain to the GAT region of an ARF effector GGA3[1].

[1]. Zhang Q, et al. Small-molecule synergist of the Wnt/beta-catenin signaling pathway. Proc Natl Acad Sci U S A. 2007 May 1;104(18):7444-8.

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