QS11 is a GTPase activating protein of ADP-ribosylation factor 1 (ARFGAP1) inhibitor that increases activity of ARFs in NIH3T3 cells at concentration of 1 μM, it also modulates Wnt/β-catenin signaling.
Both the Wnt/β-catenin signaling pathway and small GTPases of the ADP-ribosylation factors (ARF) family play important roles in regulating cell development, homeostasis and fate. QS11 is a small molecule Wnt synergist that binds to ARF GTPase-activating protein 1 (ARFGAP1) with an EC50 value of 1.5 µM. In the ARFGAP1 enzymatic assay, QS11 at 10 and 20 µM inhibited the enzymatic activity by 67% and 90%, respectively[1]. QS11 showed potent activity (EC50 = 0.5 µM) with little cytotoxicity toward HEK293 and human primary fibroblast cells. QS11 (2.5 µM) activated the Super(8X) TOPFlash reporter 200-fold in the presence of Wnt-3a CM (conditioned medium). This synergistic effect was also observed when QS11 was combined with recombinant Wnt-3a protein (10 - 200 ng/mL). When tested in a transwell cell migration assay, QS11 inhibited the migration of MDA-MB-231 cells in a dose-dependent manner, with 80% of the migration inhibited at a concentration of 2.5 µM, compared with the DMSO control. In vivo, injection of a combination of XWnt-8 RNA and QS11 induced significantly more full (20.9%) and partial (30.2%) double axis formation further supporting the notion that QS11 acts as a synergistic Wnt agonist[2].
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