Small molecules in Wnt signaling


There is significant interest in finding small molecules that can either activate or inhibit Wnt signaling. Blocking Wnt signaling, especially at the level of the nuclear complex between beta-catenin and TCF may be useful to intefere with tumor growth. The following table lists compounds that have been reported to modulate Wnt signaling by targeting various components of the pathway, resulting in either inhibition or activation (sometimes by blocking negative Wnt components). See Dodge 2010Chen 2010, Barker 2006, Meijer 2004 for reviews.

Compound

Target

Inhibitor/activator of the target

Effect on signaling

reference

WAY-316606 SFRP Inhibitor activates Bodine et al 2009
IWP Porcupine Inhibitor inhibits Chen et al (2009)
Other Porccupine inhibtorsPorcupineInhibitorInhibits

Dodge, 2012

Wang et al, 2013

LGK974PorcupineInhibitorInhibitsin trial
C59PorcupineInhibitorinhibitsProffitt et al, 2013
Ant1.4Br/Ant 1.4Cl Wnt Inhibitor (free Wnt, not membrane-bound Wnt) inhibits Morell 2008
(hetero)arylpyrimidines ? Activator activates Gilbert, 2009
Niclosamide Frizzled Inhibitor inhibits Chen 2009
apicularen and bafilomycin Vacuolar ATPase Inhibitor inhibits Cruciat 2010
XAV939 tankyrase 1/Axin Activates Axin inhibits Huang, 2009
IWR Axin Activates Axin inhibits Chen et al (2009)
IQ1 PP2A Activator activates Miyabayashi (2007)
pyrviniumCK1InhibitorinhibitsThorne (2010)
QS11 ARFGAP1 Activator activates Zhang et al 2007
NSC668036 Dsh Inhibitor inhibits Shan et al (2005)
SB-216763 GSK3 Inhibitor activates Coghlan et al (2000)
CHIR99021 GSK3 Inhibitor activates PubChem
BIO(6-bromoindirubin-3'-oxime) GSK3 Inhibitor activates Sato et al, 2004
DCA beta-catenin Activator activates Pai et al (2004
2-amino-4-[3,4-(methylenedioxy)benzyl-amino]-6-(3-methoxyphenyl)pyrimidine unknown Activator activates Liu et al (2005)
2,4-diamino-quinazoline TCF/beta-catenin Inhibitor inhibits Chen 2009
Quercetin TCF Inhibitor inhibits Park et al (2005)
ICG-001 CREB-binding protein Inhibitor inhibits Emami 2004
PKF115-584 (and several other compounds) TCF/beta-catenin Inhibitor inhibits Lepourcelet et al (2004)