TABLE 3

Extracellular targeting of the Wnt signaling pathway

InterventionUseProposed TargetEffectAffinityReference
OMP-18R5 (mAb)In vitro and in vivo (mice)FZD1, FZD2, FZD5, FZD7, FZD8Inhibition of WNT-FZD interactionn/aGurney et al. (2012)
OTSA101 (mAb) + Yttrium 90In vitro, in vivo (mice) and CTFZD10Inhibition of WNT-FZD interactionn/aFukukawa et al. (2008)
TT641 (pAb)In vitro and in vivo (mice)FZD10Inhibition of WNT-FZD interactionn/aNagayama et al. (2005)
1.99.15 (mAb)In vitro and in vivo (mice)FZD4Inhibition of WNT-FZD interactionn/aPaes et al. (2011)
pAb against FZD5In vitroFZD5Inhibition of WNT-FZD interactionn/aSen et al. (2001)
Ab against FZD7In vitro and in vivo (chick embryo)FZD7Inhibition of WNT-FZD interactionn/aPode-Shakked et al. (2011)
OMP-54F28 fusion proteinIn vitro, in vivo (mice) and CTFZD8-interacting WNT ligandsInhibition of WNT-FZD interactionn/aLe et al. (2015), Fischer et al. (2015)
Jimeno et al. (2014)
UM206In vitro and in vivo (mice)FZD1 and FZD2Inhibition of WNT-FZD interactionIC50: 2.10 nM for rFZD1;Laeremans et al. (2011)
IC50: 0.0169 nM for rFZD2Uitterdijk et al. (2016)
Foxy5 + FZD5 receptor-blocking AbIn vitro and in vivo (mice)FZD5Mimicking of WNT5A (effect independent of β-catenin)n/aSafholm et al. (2006)Safholm et al. (2008)
Box5In vitroFZD5 (?)Blockade of WNT5A signalingn/aJenei et al. (2009)
3235–0367In vitroFZD8 CRDInhibition of WNT-FZD interactionIC50: 7.1 μMLee et al. (2015)
1094–0205In vitroFZD8 CRDInhibition of WNT-FZD interactionIC50: 5 μMLee et al. (2015)
2124–0331In vitroFZD8 CRDInhibition of WNT-FZD interactionIC50: 10.4 μMLee et al. (2015)
NSC36784In vitroFZD8 CRDInhibition of WNT-FZD interactionIC50: 6.5 μMLee et al. (2015)
NSC654259In vitroFZD8 CRDInhibition of WNT-FZD interactionIC50: 5.7 μMLee et al. (2015)
NiclosamideIn vitroFZD1 (internalization)Inhibition of WNT-FZD interactionIC50: 0.5 μMChen et al. (2009b)
In vitroLRP6LRP6 degradationIC50: 0.33–0.75 μMLu et al. (2011b)
(depending on the cell line)
CurcuminIn vitroFZD1Inhibition of WNT-FZD interaction (?)n/aYan et al. (2005)
In vitroWNT3A; LRP6Inhibition of WNT-FZD interaction (?)n/aZheng et al. (2017)
In vitroWNT10B; FZD2; LRP5Enhancement of WNT-FZD interactionn/aAhn et al. (2010)
anti-Sclerostin AbIn vitroSclerostin bindingPrevention of Sclerostin-mediated disruptionn/avan Dinther et al. (2013)
to LRP5/6of LRP5/6-FZD complex formation
SalinomycinIn vitroLRP6 (?)Inhibition of WNT1/FZD5/LRP6 andIC50: 163 nM (WNT-1)Lu et al. (2011)
WNT3/FZD5/LRP6 complexes
In vitroLRP6Inhibition of WNT/FZD/LRP6 complex (?)n/aLu and Li (2014)
LeptinIn vivo (mice)LRP6; WNT4 and WNT7 (?);Enhancement of WNT4/FZD/LRP6n/aBenzler et al. (2013)
GSK-3βand WNT7A/FZD/LRP6 complexes
SilibininIn vitroLRP6Inhibition of WNT3A/FZD/LRP6 complexIC50: 34–122 μM (depending on the cell line)Lu et al. (2012)
anti-LRP6 AbsIn vitroLRP6Inhibition of WNT1 and WNT3A-mediated cascaden/aEttenberg et al. (2010)
(WNT/FZD/LRP6 complex?)
In vitroLRP6Inhibition or enhancement of WNT1/2/2B/4/6/7A/7B/8A/9B/10A/10B-mediatedn/aGong et al. (2010)
cascade (WNT/FZD/LRP6 complex?)
28aa peptideIn vitro andin vivo (mice)LRP5/6Mimicking of LRP5/6-domain → Enhancement ofn/aHay et al. (2012)
WNT signaling (via N-cadherin)
DKK1 and DKK2In vivo (Xenopus embryos)LRP6Inhibition of WNT signalingn/aMao et al. (2001)
anti-DKK1 AbIn vitro and in vivo (mice)DKK1Neutralization of DKK1 → Enhancement of WNT signalingn/aSato et al. (2010b)
BHQ880 mAbIn vitro, in vivo (mice) and CTDKK1Neutralization of DKK1 → Enhancement of WNT signalingn/aFulciniti et al. (2009)
Iyer et al. (2014)
DKK1 vaccineIn vivo (mice)DKK1Enhancement of DKK1 levels → Inhibition of WNT signalingn/aQian et al. (2012)
Iminooxothiazolidines (Compounds 1–34)In vitrosFRP1Inhibition of sFRP1 → Enhancement of WNT signalingEC50: 7.2 μM (Compound 1)Shi et al. (2009)
WAY-316606In vitrosFRP1Inhibition of sFRP1 → Enhancement of WNT signalingIC50: 0.5 μMBodine et al. (2009)
EC50: 0.65 μMMoore et al. (2010)
N-substituted piperidinylIn vitrosFRP1Inhibition of sFRP1 → Enhancement of WNT signalingIC50: 0.04–0.87 μMMoore et al. (2010)
diphenylsulfonyl sulfonamidesED50: 0.07–1.9 μM