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Table 2 Wnt inhibiting molecules for disease

From: Wnt signaling in colorectal cancer: pathogenic role and therapeutic target

No.

Abbreviated name

Full official name

Classification

Intervention mechanism

References

1

ACBP

Anticancer bioactive peptide

Novel bioactive peptide

ACBP can inhibit phospho-LRP6 and stimulate phospho-β-catenin.

[168]

2

ND

MiR-377-3p

MicroRNA

Directly target ZEB2 and XIAP to inhibit Wnt/β-catenin signaling

[169]

3

DHME

Dehydroxyhispolon methyl ether

Hispolon derivatives

Inhibits β-catenin-mediated T cell factor (TCF)-dependent transcriptional activity

[170]

4

ND

SSTC3

New small molecule CK1α activator

The target CK1α inhibits the growth of mouse CRC xenografts and attenuates the growth of patient-derived metastatic CRC xenografts

[171]

5

CQD

Chlorquinaldol

Bacteriostatic agent

Inhibit the acetylation of β-catenin, destroy the interaction between β-catenin and T cell factor 4 (TCF4), and reduce the binding of β-catenin to Wnt target gene promoters, and down-regulate the expression of these target genes

[172]

6

ND

KY7749

Compound

Inhibit the proliferation and transformation of CRC cells, independently of β-catenin degradation of Ras

[173]

7

ND

Niclosamide

Antihelminth compound

Inhibit Wnt/β-catenin pathway activation, down-regulate Dvl2, and reduce downstream β-catenin signal transduction

[174]

8

ND

KHDRBS3

Genes encoding KH RNA binding domains, signal transduction related 3

KHDRBS3 may play a key role in acquiring stem cell characteristics (such as drug resistance and spheroid/organoid formation) by regulating the expression of CD44 variants and the Wnt signaling pathway

[175]

9

ND

KYA1797K

Compound

GSK3β activates small molecules that degrade β-catenin and Ras, inhibits KRAS mutations, and reduces β-catenin, RAS and EGFR levels by targeting the Wnt/β-catenin pathway

[176]

10

ND

MiR-506

MicroRNA

Inhibit MDR1/P-gp expression by down-regulating the Wnt/β-catenin pathway

[177]

11

ND

MiR-148a

MicroRNA

Suppresses the expression of WNT10b and β-catenin signaling, and suppresses the expression of stem cells.

[178]

12

MAGI1

MAGUK with inverted domain structure-1

Scaffold protein

Stabilize the location of E-cadherin and β-catenin at the cell-cell junction, enhance the formation of actin stress fibers and adhesion plaques, increase cell adhesion to matrix proteins and inhibit Wnt signaling, independent of adhesion Growth, in vitro migration and invasion

[179]

13

ND

BMP7v

Bone morphogenetic proteins

BMP7v treatment promotes CR-CSC differentiation and reproduces cell differentiation-related gene expression profiles by inhibiting Wnt pathway activity and reducing the mesenchymal characteristics and survival of CR-CSC

[180]

14

NSAID

Sulindac on nuclear

Nonsteroidal anti-inflammatory drugs

Eliminates β-catenin/TCF-mediated transcription in CRC cell lines DLD1 and SW480, and reduces the level of non-phosphorylated β-catenin

[181]

15

4βHWE

4β-Hydroxywithanolide E

Novel Antagonist of Wnt Signaling

Promote the phosphorylation and degradation of β-catenin, and subsequently inhibit its nuclear translocation, mediate G0/G1 cell cycle arrest and apoptosis, and weaken the Wnt/β-catenin signaling pathway

[182]

16

ND

HGC33-SFB-NP

HGC33 modified NPs

Inhibit Wnt-induced signal transduction, and inhibit G0/1 cells down-regulating the expression of cyclin D1, thereby inhibiting epithelial-mesenchymal transition

[183]

17

Si-WNT8b

Small interfering RNA against WNT8b

Small interfering RNA against WNT8b

Reduces the levels of WNT8b, frizzled-4, β-catenin, phosphorylated GSK-3β (p-GSK-3β) and cyclin-D, while it increases the levels of p-β-catenin and GSK-3β

[184]

18

ND

lncRNA DANCR

Long non-coding RNAs

Significantly reduces the expression levels of p-GSK-3β and β-catenin, and inhibits the activation of Wnt/β-catenin signaling pathway

[185]

19

plopP

Inorganic polyphosphate

Phosphate Compound

Mediates cyclin D1 expression and nuclear localization are IKKÉ‘ and ERK1/2 dependent

[186]

20

ND

AC007271.3

Long noncoding RNA

Promote OSCC cell proliferation, invasion and inhibit cell apoptosis through Wnt/β-catenin signaling pathway

[187]

21

CORM2

CO-releasing molecule 2

Exogenous small molecules

Significantly reduce cell apoptosis, cytochrome release from mitochondria to cytoplasm, MPTP opening and caspase-3 cleavage, inhibition of superoxide anion generation in the response of HUVECs to ox-LDL and Wnt/β-catenin pathway activation

[188]

22

ND

VALD-3

Schiff base compounds

Inhibition of Wnt/β-catenin signaling pathway induces apoptosis and cell cycle arrest in human cancer cells

[189]

23

CDK14

Cyclin-dependent kinase 14

Protein kinase

CDK14 inhibition mediated Wnt signaling pathway can inhibit cancer cell proliferation, invasion and migration

[190]

24

ND

FL118

A novel camptothecin analogue

Significantly inhibits the expression of vimentin, and at the same time enhances the expression of E-cadherin. It is detected that the expression of β-catenin and its target survivin and cyclin D1 are reduced

[191]

25

ND

Prednisolone

Glucocorticoid

It is possible to inhibit Wnt signaling by inhibiting the co-receptor of the Wnt/β-catenin signaling pathway in the early stage of glucocorticoid therapy and inhibiting its ligand in the following weeks

[192]

26

ND

3-Cl-AHPC

Adamantyl-substituted retinoid-related

Inhibit Wnt/β-catenin pathway, reduce β-catenin nuclear localization and inhibit Wnt/β-catenin activation of transcription factor TCF/LEF

[193]

27

ND

MiR-603

MicroRNA

Overexpression promotes nuclear β-catenin levels and TOPflash luciferase activity, and activates the Wnt/β-catenin signaling pathway

[194]

28

ND

IWP-2

A Wnt signal inhibitor

Improve neuropathic pain by inhibiting Wnt/β-catenin pathway

[195]

29

ND

RBM5

RNA binding motif protein

By inhibiting Wnt/β-catenin signal transduction and inducing cell apoptosis

[196]

30

ND

MiR-384

MicroRNA

Targets Smad5 and inactivates the Wnt/β-catenin pathway

[197]

31

ND

b-AP15

Inhibitor of the ubiquitin-specific peptidase 14

Increase endoplasmic reticulum stress/UPR and inhibit Wnt/Notch1 signaling pathway

[198]

32

ND

MiR-20b

MicroRNA

May inhibit APC through canonical Wnt signaling pathway

[199]

33

ND

Hsa_circ_0004018

Circular RNA

Targeting miR-626/ inhibits Wnt/β-catenin signaling pathway, blocking the growth of xenograft tumors in vivo

[200]

34

ND

Lanatoside C

Cardiac glycosides

Blocking the MAPK/Wnt/PAM signaling pathway prevents the G2/M phase of the cell cycle from exerting its anti-cancer activity

[201]

35

ND

MiR-216a

MicroRNA

Demethylated miR-216a down-regulates HMGB3 and inhibits cell proliferation, migration and invasion. Inhibition of HMGB3 expression can induce apoptosis, inhibit cell proliferation, and down-regulate Wnt/β-catenin pathway activity.

[202]

36

ND

MiR-375-3p

MicroRNA

Directly inhibit the expression of FZD8 to block the Wnt/β-catenin pathway and downstream molecules Cyclin D1 and c-Myc, which can increase the expression of caspase 1 and caspase 3, and promote T24 cell apoptosis

[203]

37

ND

TIPE1

TNFAIP8

Significantly inhibits the expression and activity of MMP2 and MMP9, and mediates Wnt/β-catenin signaling

[204]

38

ANP

Atrial natriuretic peptide

Small peptide

Triggers NHE-1 mediated increase in intracellular acidity, through Frizzled-mediated activation, which acts on the upstream of the cascade, while EIPA acts on the downstream to inhibit Wnt/ β-catenin signaling

[205]

39

BI

Benzyl isothiocyanate

ND

Targeting undifferentiated CSC reduces the number of cells containing β-catenin in the nucleus

[206]

40

PI

Phenethylisothiocyanate

ND

Reduce the number of cells containing β-catenin in the nucleus, effectively inhibit the growth of multicellular tumor spheroid models that mimic micrometastasis

[206]

41

ND

MiR-624-5p

MicroRNA

Induce cell senescence, block the growth of experimental HBL, and directly target the 3′-untranslated region of β-catenin

[207]

42

ND

Z-Ajoene

ND

Promote the phosphorylation of β-catenin at Ser45 in a casein kinase 1α (CK1α)-dependent manner

[208]

43

TgROP18

ROP18 from T. gondii

Toxoplasma

Specific binding of different host immune-related molecules to mediate the suppression of host innate and adaptive immune response

[209]

44

ND

RIG-3

Cell surface Ig superfamily proteins

Inhibition of CAM-1, a Ror type receptor tyrosine kinase that binds to Wnt ligands, regulates Wnt signaling

[210]

45

ND

Pyrvinium

Small molecule

Increase the proliferation of MSC while inhibiting its osteogenic and chondrocyte lineages by reducing cytoplasmic β-catenin

[211]

46

ND

LiCl

Small molecule

Inhibition of GSK-3beta promotes canonical Wnt signaling, increases β-catenin nuclear translocation and upregulates the transcriptional activity of canonical Wnt-responsive promoters

[212]

47

TZDs

Thiazolidinediones

Small molecule

Down-regulate DNA synthesis in MDA-MB-231 and T47D, and reduce Wnt co-receptor frizzled-1 and low-density lipoprotein-related protein 6 (LRP6) mRNA expression and LRP6. Targeting downstream Wnt signaling molecules in T47D cells, down-regulating p-β-catenin (S33/S37/T41) and promoting β-catenin translocation into the nucleus

[213]

48

ND

MiR-376c

MicroRNA

Targeting Wnt-3, ARF-GEF-1 inhibits ARF-6 activation, thereby preventing the release of β-catenin and its transactivation, thereby inhibiting osteoblast differentiation

[214]

49

SKI II

SphK1 inhibitor II

Inhibitor

Mediates β-catenin degradation through Wnt5A

[215]

50

ND

MiR-376c

MicroRNA

Inhibit YTHDF1 expression and Wnt/β-catenin pathway induction

[216]

51

Li

Lithium

Small molecule

Significantly inhibits BMP-2’s stimulation of cartilage formation and GSK-3beta enzyme activity, and reduces the levels of N-cadherin and mRNA, and reduces the total level of LEF-1 and β-catenin by BMP-2 Up-regulation of nuclear levels reduces the interaction of β-catenin with GSK-3beta

[217]

52

ND

SP600125

JNK inhibitor

Prevents Wnt5a-induced CXCR4 expression and cell migration in SFRP5-negative cells

[218]

53

ND

FH535

Wnt signaling pathway inhibitor

Regulate the expression of CyclinA2 and Claudin1 genes to inhibit the proliferation and migration of colorectal cancer cells, and down-regulate β-catenin

[219]

54

CEACAM1

Cell adhesion molecule 1

Cell adhesion molecule

Site-specific regulation of β-catenin phosphorylation to control EMT

[220]

55

PBN

Probenecid

Small molecule

Blocking the PANX1 channel reduces the release of ATP in A375-P cells and reduces β-catenin levels

[221]

56

CPX

Ciclopirox

Small molecule

Inhibit cell proliferation, induce cell apoptosis, inhibit cell migration and invasion, inhibit angiogenesis and lymphangiogenesis to exert its anti-cancer activity, and mediate Wnt/β-catenin signal transduction

[222]

57

ND

Anti-IL-3R-EVs

Inhibitor

MiR-214-3p, which directly targets β-catenin, was upregulated, while miR-24-3p, which targets adenomatous polyposis (APC) and glycogen synthase kinase-3β (GSK3β), was found to be downregulated

[223]

58

ND

E-cadherin

Cadherin

Inhibit the cell surface localization of endogenous M-cadherin and N-cadherin, as well as cell-cell fusion, dominant negative β-catenin mutant, and inhibit Wnt/β-catenin signaling

[224]

59

W9

WP9QY

Peptides

Inhibition of Wnt/β-catenin signaling inhibits osteoclast production and enhances osteoblast production by reducing the expression of sclerostin in alveolar bone

[225]

60

ND

Collagen XVIII

Collagen

The long isoform contains a coiled (Fz) domain with Wnt inhibitory activity, which can inhibit the migration and proliferation of endothelial cells or induce their death to effectively reduce tumor angiogenesis and growth

[226]

61

ND

lncRNA BCYRN1

lncRNA

Inhibit Wnt/−catenin pathway to inhibit cell proliferation and migration and induce apoptosis

[227]

62

Box 5

N-butyloxycarbonyl hexapeptide

Peptides

Directly inhibit Wnt5a-induced protein kinase C and Ca(2+) signals

[228]

63

ND

Receptor tyrosine kinase Ror2

Kinase

Activating the Wnt-JNK pathway and inhibiting the β-catenin-TCF pathway play an important role in mediating non-canonical Wnt5a signaling

[229]

64

ND

Phosphoprotein phosphatase-2A

Phosphatase

Inhibit Wnt3a

[230]

65

MIR155 HG

MIR155 host gene

Long noncoding RNA

Inhibit the production of its derivatives miR-155-5p and miR-155-3p, and reduce the small interfering RNA. MIR155HG can inhibit cell proliferation, migration, invasion and in situ glioma growth, and target the inhibition of Wnt/β-catenin pathway

[231]

66

ND

XAV939

A small inhibiter

Inhibition of tankyrase and subsequent stabilization of cytoplasmic axin levels strongly inhibits the Wnt pathway

[232]

67

TSK

Tsukushi

Small leucine-rich proteoglycan family

inhibits signaling molecules, such as BMP and Wnt

[233]

68

ND

HDAC-inhibitor

Inhibitor

Decreases the number/activity of β-catenin transcription factor, which promotes cell growth arrest by reducing the expression of c-Myc and cyclin D1 and eliminating the pro-survival Wnt/β-catenin signaling pathway

[234]