Triptonide(NSC 165677; PG 492), extracted from Tripterygium wilfordii Hook, inhibited the proliferation of mouse splenocytes induced by suboptimal concentration of concanavalin A or lipopolysaccharide at concentrations of 0.02, 0.1, and 0.5 mg/ml.
IWP-2-V2 is a IWP-2 (HY-13912) analogue that retains activity against the Wnt/β-catenin pathway[1].
IWR-1 is a tankyrase inhibitor which inhibits Wnt/β-catenin signaling pathway.
Wnt/β-catenin agonist 4 (Derivative 83) is an agonist of Wnt that activates Wnt/β-catenin signal transmission[1].
NC-043 (15-Oxospiramilactone) is a diterpenoid derivative inhibitor of Wnt/β-catenin signaling that interferes with the β-catenin/TCF4 association; decreases the mRNA and/or protein expression of Wnt target genes Axin2, Cyclin D1 and Survivin in SW480 cells, inhibits anchorage-independent growth and xenograft tumorigenesis in vitro and in vivo; inhibits canonical Wnt signaling downstream of β-catenin stability, causes G2/M arrest and inhibits colon cancer cell growth.
Berberine has shown to be effective in inhibiting cell proliferation and promoting apoptosis in various cancerous cells; MAPK and Wnt/β-catenin pathways affected by Berberine.IC50 value:Target: Anticancer agentThe plant-based alkaloid berberine has potential therapeutic applications for breast cancer, although a better understanding of the genes and cellular pathways regulated by this compound is needed to define the mechanism of its action in cancer treatment. In this review, the molecular targets of berberine in various cancers, particularly breast cancer, are discussed. Berberine was shown to be effective in inhibiting cell proliferation and promoting apoptosis in various cancerous cells. Some signaling pathways affected by berberine, including the MAP (mitogen-activated protein) kinase and Wnt/β-catenin pathways, are critical for reducing cellular migration and sensitivity to various growth factors [1]. Treatment with BBR(Berberine) in rats on the atherogenic diet reduced plasma total cholesterol and nonHDL cholesterol levels by 29%-33% and 31%-41%, respectively, with no significant differences being observed among the three doses [2]. Berberine induced both apoptotic and autophagic death of HepG2 cells, which was associated with a significant activation of AMPK and an increased expression of the inactive form of acetyl-CoA carboxylase (ACC) [3]. Berberine did not show major effects on viability of HEK-293 embryonic kidney and HCT116 colon carcinoma cells and was not toxic in concentrations up to 20 μM. Berberine inhibited β-catenin transcriptional activity and attenuated anchorage-independent growth. As a result of berberine treatment, cellular levels of active β-catenin were reduced concomitant with an increase in the expression of E-cadherin [4].
Vantictumab (OMP-18R5) is a fully human IgG2 monoclonal antibody. Vantictumab inhibits Wnt pathway signaling by binding to FZD1/2/5/7/8 receptors. Vantictumab is being studied against cancers such as metastatic HER2-negative breast cancer and metastatic pancreatic adenocarcinoma[1][2].
N-(3-Methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide is a macamide isolated from Maca (Lepidium meyenii Walp.) N-(3-Methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide induces mesenchymal stem cells osteogenic differentiation and consequent bone formation through activating the canonical Wnt/β‐catenin signaling pathway. N-(3-Methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide can be used for the research of osteoporosis[1].
Wnt pathway activator 2 is a potent Wnt activator extracted from patent WO2012024404A1, compound 2, has an IC50s of 13 nM[1].
β-catenin/CBP-IN-1 (CBP/β-catenin inhibitor) is a potent and selective CBP/β-catenin inhibitor, extracted from the patent WO2014092154A1. β-catenin/CBP-IN-1 has the potential for the study of liver fibrosis induced by hepatitis virus[1].
BML-284 is selective and cell-permeable Wnt signaling activator.
KY-02327 is an orally active, small molecule inhibitor of the Dishevelled (Dvl)-CXXC5 interaction with IC50 of 3.1 uM, a metabolically stabilized KY-02061 analog; KY-02327 is more stable by 2.3-fold and 1.3-fold than KY-02061 in rat liver microsomes and in human hepatocytes, respectively; shows enhanced effect on induction of ALP activity of osteoblast cells compared with KY-02061; activates the Wnt/β-catenin pathway, promotes osteoblast differentiation, and rescues BMD, bone volume, and trabecular bone structures in variectomized (OVX) mouse model.
RA-V is a cyclic hexapeptide. RA-V has activity against Wnt, Myc and Notch with IC50 values of 50, 75, and 93 ng/mL, respectively. RA-V can be used for the research of cancer-related signaling pathways.
Zamaporvint (RXC004) is an orally active and selective inhibitor of Wnt. Zamaporvint targete membrane-bound o-acyltransferase Porcupine and inhibited Wnt ligand palmitoylation, secretion, and pathway activation. Zamaporvint displays a favorable pharmacokinetic profile and shows potent antiproliferative effects in Wnt ligand-dependent colorectal and pancreatic cell lines. Zamaporvint possesses multiple antitumor mechanisms and can be used in cancer research[1].
TNIK-IN-5 is an efficient TNIK inhibitor with IC50 of 0.05 μM. TNIK-IN-5 efficiently inhibits Wnt signaling in intact cells. TNIK-IN-5 shows excellent in vitro anti-colorectal cancer activity[1].
Wogonin is a naturally occurring mono-flavonoid, can inhibit the activity of CDK8 and Wnt, and exhibits anti-inflammatory and anti-tumor effects.
Wnt pathway activator 1 is a potent Wnt activator extracted from patent WO2012024404A1, compound 1, has an IC50s of 28-29 nM[1].
Coronaridine, an iboga type alkaloid, inhibits the wnt signaling pathway by decreasing β-catenin expression[1].
ABC99 is an N-hydroxyhydantoin (NHH) carbamate that selectively inhibits the Wnt-deacylating enzyme NOTUM (IC50=13 nM). ABC99 preserves Wnt3A signaling in the presence of NOTUM[1].
PNU-74654 is an inhibitor of Wnt/β-catenin pathway with an IC50 of 129.8 μM in NCI-H295 cell.
A negative allosteric modulator of the Frizzled4 (Fzd4) receptor and a Wnt/β-catenin pathway inhibitor with pEC50 value of 5.74 for inhibition of Wnt antagonism; induces conformational changes in Fz4 by interacting with the third intracellular loop, ICL3, inhibiting binding of dishevelled (Dsh) and hampering the formation of the Fz4-Dsh complex that is necessary for β-catenin nuclear transport and ultimately transcription of TCF/LEF-regulated genes.
SEN461 is a wnt inhibitor.
WIKI4 is a potent inhibitor of Wnt/β-catenin signaling (EC50 ~ 75 nM); inhibits auto-ADP-ribosylation of tankyrase 2 (TNKS2) (IC50 ~15 nM).
KYA1797K is a potent and selective Wnt/β-catenin inhibitor with an IC50 of 0.75 µM.
FIDAS-3 is a stilbene derivative and is a potent Wnt inhibitor with an IC50 of 4.9 μM for methionine S-adenosyltransferase 2A (MAT2A). FIDAS-3 effectively competes against S-adenosylmethionine (SAM) for MAT2A binding. FIDAS-3 has anticancer activities[1][2].
YW1128 is an inhibitor of Wnt/��-catenin signaling with an IC50 value of 4.1 nM in a reporter assay.
CWP232228, a highly potent selective Wnt/β-catenin signaling inhibitor, antagonizes binding of β-catenin to T-cell factor (TCF) in the nucleus. CWP232228 suppresses tumor formation and metastasis without toxicity through the inhibition of the growth of breast and liver cancer stem cells (CSCs)[1].
Foxy-5 is a mimicking peptide of WNT5A which is a non-canonical member of the Wnt family. Foxy-5 is a WNT5A agonist and effectively reduces the metastatic spread of WNT5A-low prostate cancer cells in an orthotopic mouse model[1][2].
NSC260594 (NSC 260594) is a specific inhibitor of HIV-1 RNA packaging, which involves preventing the interaction of Gag with SL3 by stabilizing this small RNA stem-loop which then leads to stabilization of the global packaging signal region (psi or ψ); specifically blocks HIV-1 RNA encapsidation, binds to HIV-1 gRNA and exhibits potent antiviral activity; NSC260594 also is a small molecule inhibitor of the Escherichia coli condensin MukBEF, affects MukB directly.
Heparan sulfate, a complex and linear polysaccharide, exists as part of glycoproteins named heparan sulfate proteoglycans, which are expressed abundantly on the cell surface and in the extracellular matrix.