Description
QS11 is an inhibitor of GTPase activating protein of ADP-ribosylation factors (ARFGAPs) that increases activity of ARFs in NIH3T3 cells at a concentration of 1 μM. It activates Wnt/β-catenin activity in a reporter assay using HEK293 cells (EC50 = 0.5 μM). QS11 exhibits synergy with Wnt-3a ligand-conditioned media, inducing a 200-fold increase in reporter activity compared to 40- and 2-fold increases observed with Wnt-3a ligand-conditioned media alone or QS11 treatment alone, respectively. It inhibits ARFGAP1 with an EC50 value of 1.5 μM in an enzyme assay and inhibits the migration of MDA-MB-231 breast cancer cells that overexpress AMAP1, an ARFGAP essential to cellular invasiveness.
Uses
QS 11 is a small molecule Wnt synergistic agonist.
Definition
ChEBI: (2S)-2-[[2-(2,3-dihydro-1H-inden-5-yloxy)-9-[(4-phenylphenyl)methyl]-6-purinyl]amino]-3-phenyl-1-propanol is a member of biphenyls.
in vitro
qs11 showed potent wnt synergist activity with little cytotoxicity in hek293 cells (ec50 = 0.5 μm) and human primary fibroblast cells (ec50 ≥ 10 μm). qs11 at 2.5 μm activated the super(8x)topflash reporter ~200-fold in the presence of wnt-3a conditioned medium. synergistic effect was also observed when qs11 was combined with recombinant wnt-3a protein (10–200 ng/ml) [2].
in vivo
in wnt signaling test model, embryos were injected with qs11, xwnt-8 rna or a combination of qs11and xwnt-8 rna. compared with qs11 alone and xwnt-8 rna alone, injection of a combination of xwnt-8 rna and qs11 induced significantly more full (20.9%) and partial (30.2%) double axis formation [2]..
References
[1] singh mk1, gao h1, sun w1, song z1, schmalzigaug r2, premont rt2, zhang q3. structure-activity relationship studies of qs11, a small molecule wnt synergistic agonist. bioorg med chem lett. 2015 nov 1;25(21):4838-42.
[2] zhang q1, major mb, takanashi s, camp nd, nishiya n, peters ec, ginsberg mh, jian x, randazzo pa, schultz pg, moon rt, ding s. small-molecule synergist of the wnt/beta-catenin signaling pathway. proc natl acad sci u s a. 2007 may 1;104(18):7444-8. epub 2007 apr 25.
