TABLE 3.

Extracellular targeting of the Wnt signaling pathway

Intervention	Use	Proposed Target	Effect	Affinity	Reference
OMP-18R5 (mAb)	In vitro and in vivo (mice)	FZD1, FZD2, FZD5, FZD7, FZD8	Inhibition of WNT-FZD interaction	n/a	Gurney et al. (2012)
OTSA101 (mAb) + Yttrium 90	In vitro, in vivo (mice) and CT	FZD10	Inhibition of WNT-FZD interaction	n/a	Fukukawa et al. (2008)
TT641 (pAb)	In vitro and in vivo (mice)	FZD10	Inhibition of WNT-FZD interaction	n/a	Nagayama et al. (2005)
1.99.15 (mAb)	In vitro and in vivo (mice)	FZD4	Inhibition of WNT-FZD interaction	n/a	Paes et al. (2011)
pAb against FZD5	In vitro	FZD5	Inhibition of WNT-FZD interaction	n/a	Sen et al. (2001)
Ab against FZD7	In vitro and in vivo (chick embryo)	FZD7	Inhibition of WNT-FZD interaction	n/a	Pode-Shakked et al. (2011)
OMP-54F28 fusion protein	In vitro, in vivo (mice) and CT	FZD8-interacting WNT ligands	Inhibition of WNT-FZD interaction	n/a	Le et al. (2015), Fischer et al. (2015)
					Jimeno et al. (2014)
UM206	In vitro and in vivo (mice)	FZD1 and FZD2	Inhibition of WNT-FZD interaction	IC50: 2.10 nM for rFZD1;	Laeremans et al. (2011)
				IC50: 0.0169 nM for rFZD2	Uitterdijk et al. (2016)
Foxy5 + FZD5 receptor-blocking Ab	In vitro and in vivo (mice)	FZD5	Mimicking of WNT5A (effect independent of β-catenin)	n/a	Safholm et al. (2006)Safholm et al. (2008)
Box5	In vitro	FZD5 (?)	Blockade of WNT5A signaling	n/a	Jenei et al. (2009)
3235–0367	In vitro	FZD8 CRD	Inhibition of WNT-FZD interaction	IC50: 7.1 μM	Lee et al. (2015)
1094–0205	In vitro	FZD8 CRD	Inhibition of WNT-FZD interaction	IC50: 5 μM	Lee et al. (2015)
2124–0331	In vitro	FZD8 CRD	Inhibition of WNT-FZD interaction	IC50: 10.4 μM	Lee et al. (2015)
NSC36784	In vitro	FZD8 CRD	Inhibition of WNT-FZD interaction	IC50: 6.5 μM	Lee et al. (2015)
NSC654259	In vitro	FZD8 CRD	Inhibition of WNT-FZD interaction	IC50: 5.7 μM	Lee et al. (2015)
Niclosamide	In vitro	FZD1 (internalization)	Inhibition of WNT-FZD interaction	IC50: 0.5 μM	Chen et al. (2009b)
	In vitro	LRP6	LRP6 degradation	IC50: 0.33–0.75 μM	Lu et al. (2011b)
				(depending on the cell line)
Curcumin	In vitro	FZD1	Inhibition of WNT-FZD interaction (?)	n/a	Yan et al. (2005)
	In vitro	WNT3A; LRP6	Inhibition of WNT-FZD interaction (?)	n/a	Zheng et al. (2017)
	In vitro	WNT10B; FZD2; LRP5	Enhancement of WNT-FZD interaction	n/a	Ahn et al. (2010)
anti-Sclerostin Ab	In vitro	Sclerostin binding	Prevention of Sclerostin-mediated disruption	n/a	van Dinther et al. (2013)
		to LRP5/6	of LRP5/6-FZD complex formation
Salinomycin	In vitro	LRP6 (?)	Inhibition of WNT1/FZD5/LRP6 and	IC50: 163 nM (WNT-1)	Lu et al. (2011)
			WNT3/FZD5/LRP6 complexes
	In vitro	LRP6	Inhibition of WNT/FZD/LRP6 complex (?)	n/a	Lu and Li (2014)
Leptin	In vivo (mice)	LRP6; WNT4 and WNT7 (?);	Enhancement of WNT4/FZD/LRP6	n/a	Benzler et al. (2013)
		GSK-3β	and WNT7A/FZD/LRP6 complexes
Silibinin	In vitro	LRP6	Inhibition of WNT3A/FZD/LRP6 complex	IC50: 34–122 μM (depending on the cell line)	Lu et al. (2012)
anti-LRP6 Abs	In vitro	LRP6	Inhibition of WNT1 and WNT3A-mediated cascade	n/a	Ettenberg et al. (2010)
			(WNT/FZD/LRP6 complex?)
	In vitro	LRP6	Inhibition or enhancement of WNT1/2/2B/4/6/7A/7B/8A/9B/10A/10B-mediated	n/a	Gong et al. (2010)
			cascade (WNT/FZD/LRP6 complex?)
28aa peptide	In vitro andin vivo (mice)	LRP5/6	Mimicking of LRP5/6-domain → Enhancement of	n/a	Hay et al. (2012)
			WNT signaling (via N-cadherin)
DKK1 and DKK2	In vivo (Xenopus embryos)	LRP6	Inhibition of WNT signaling	n/a	Mao et al. (2001)
anti-DKK1 Ab	In vitro and in vivo (mice)	DKK1	Neutralization of DKK1 → Enhancement of WNT signaling	n/a	Sato et al. (2010b)
BHQ880 mAb	In vitro, in vivo (mice) and CT	DKK1	Neutralization of DKK1 → Enhancement of WNT signaling	n/a	Fulciniti et al. (2009)
					Iyer et al. (2014)
DKK1 vaccine	In vivo (mice)	DKK1	Enhancement of DKK1 levels → Inhibition of WNT signaling	n/a	Qian et al. (2012)
Iminooxothiazolidines (Compounds 1–34)	In vitro	sFRP1	Inhibition of sFRP1 → Enhancement of WNT signaling	EC50: 7.2 μM (Compound 1)	Shi et al. (2009)
WAY-316606	In vitro	sFRP1	Inhibition of sFRP1 → Enhancement of WNT signaling	IC50: 0.5 μM	Bodine et al. (2009)
				EC50: 0.65 μM	Moore et al. (2010)
N-substituted piperidinyl	In vitro	sFRP1	Inhibition of sFRP1 → Enhancement of WNT signaling	IC50: 0.04–0.87 μM	Moore et al. (2010)
diphenylsulfonyl sulfonamides				ED50: 0.07–1.9 μM