FH535 is an inhibitor of Wnt/β-catenin and PPAR, with anti-tumor activities.
IQ 1 has many functions such as decreasing Wnt-stimulated phosphorylation, maintaining the pluripotency of murine ESCs, preventing PP2A/Nkd interaction and so on.IQ 1 maintains the pluripotency of murine ESCs in long-term culture in a Wnt-dependent manner. IQ 1 decreased Wnt-stimulated phosphorylation of p300 at Ser-89.IQ-1 binds to serine/threonine phosphatase PP2A and prevents PP2A/Nkd interaction.The binding of IQ 1 to PR72/130 leads to decreased phosphorylation of the coactivator protein p300 at Ser-89. IQ 1 thereby diminishes the β-catenin/p300 interaction and prevents β-catenin coactivator switching from CBP to p300.
UU-T02 is a novel potent, selective small-molecule inhibitor of β-catenin/Tcf4 interaction with Ki of 1.36 uM; displays 63-fold and 175-fold selectivity over β-catenin/E-cadherin and β-catenin/APC interactions, respectively.
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].
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].
Coronaridine, an iboga type alkaloid, inhibits the wnt signaling pathway by decreasing β-catenin expression[1].
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.
KY1022 is a ras destabilizer. KY1022 targets the Wnt/ß-catenin pathway and inhibits development of metastatic colorectal cancer.
Gallocyanine chloride, a synthetic blue dyestuff, blocks DKK1 inhibitory activity by disrupting DKK1/LRP6 interaction. Its association with LRP6 is weak (IC50 of about 3 μM in the inhibition of DKK1 binding). Gallocyanine dye acts as a potential agent for the research of Alzheimer's disease and related neurodegenerative tauopathies[1].
Specnuezhenide ((8E)-Nuezhenide) is isolated from the fruits of Ligustrum lucidum. Specnuezhenide ((8E)-Nuezhenide) can inhibit IL-1β-induced inflammation in chondrocytes via inhibition of NF-κB and wnt/β-catenin signaling. Specnuezhenide ((8E)-Nuezhenide) exerts anti-inflammatory effects in a rat model of osteoarthritis (OA)[1].
IWP-4 is a small molecule Wnt inhibitor with an IC50 of 25 nM.
KY-05009 is an ATP-competitive Traf2- and Nck-interacting kinase (TNIK) inhibitor with a Ki of 100 nM. KY-05009 pharmacologically inhibits TGF-β1-induced epithelial-to-mesenchymal transition (EMT) in human lung adenocarcinoma cells. KY-05009 inhibits the protein expression of TNIK and transcriptional activity of Wnt target genes and induces apoptosis in cancer cells. KY-05009 exerts anti-cancer activity[1].
F7H is a Frizzled receptor FZD7 antagonist (IC50: 1.25 μM). Frizzled receptors (FZDs) influence Wnt signaling, mediating embryonic development and tissue homeostasis. F7H is a potent ligand for the FZD7 transmembrane domain (TMD)[1].
KY1220 is a compound that destabilizes both β-catenin and Ras, via targeting the Wnt/β-catenin pathway; with an IC50 of 2.1 μM in HEK293 reporter cells.
ARUK3001185 (Compound 8l) is a potent, selective, orally active and brain-penetrant inhibitor of Notum activity with an IC50 of 6.7 nM[1].
SKL2001 is an agonist of the Wnt/β-catenin pathway, with anti-cancer activity.
SSTC3 is a novel small-molecule CK1α activator with EC50 of 30 nM (WNT-driven reporter gene assay), Kd of 32 nM; has better pharmacokinetic properties than pyrvinium, attenuates the growth of such Apc mutant organoids with EC50 of 2.9 uM; decreases the viability of the WNT-dependent cell lines (EC50 = 132, 63, and 123 nM for HT29, SW403, and HCT116 cells, respectively), inhibits the growth of CRC xenografts in mice; also attenuates the growth of patient-derived metastatic CRC xenograft, with minimal gastrointestinal toxicity compared to other classes of WNT inhibitors.
Methyl vanillate, one of the ingredients in Hovenia dulcis Thunb, is a Wnt/β-catenin pathway activator[1]. A benzoate ester that is the methyl ester of vanillic acid. It has a role as an antioxidant and a plant metabolite.
Ipafricept (OMP-54F28; FZD8-Fc) is the first class of recombinant fusion proteins, consisting of the extracellular portion of the human fried-8 receptor fused to the Fc fragment of human IgG1 binding to the Wnt ligand. Ipafricept shows solid tumor inhibition activity, with well tolerance[1].
JW67 inhibits the canonical Wnt signaling with an IC50 of 1.17μM[1]. JW67 affects the multiprotein complex consisting of β-catenin/GSK-3β/AXIN/APC/CK1 that rapidly reduces active β-catenin with a subsequent downregulation of Wnt target genes. JW67 also inhibits colorectal cancer cell growth[1].
Sempervirine is an alkaloid derived from Gelsemium elegans Benth.. Sempervirine inhibits the proliferation of hepatocellular carcinoma (HCC) cells and induces apoptosis by regulating Wnt/β-catenin pathway[1].
ICG-001 is an inhibitor of β-catenin/TCF mediated transcription. It works by specifically binding to cyclic AMP response element-binding protein with an IC50 of 3 μM.
FzM1.8 derives from FzM1, is an allosteric agonist of FZD4 with pEC50 of 6.4. FzM1.8 binds to FZD4 and activates the WNT/β-catenin pathway, by promoting TCF/LEF transcriptional activity in the absence of any WNT ligand. FzM1.8 binding stabilizes FZD4 with an increased affinity for heterotrimeric G protein and stimulates the release of the Gβγ subunit that in turn activates PI3K[1].
Windorphen is a Wnt/β-catenin signal inhibitor that specifically targets the function of the c-terminal transactivation domain of β-catenin-1 but not β-catenin-2. Windorphen selectively targets p300, disrupting the association of the mammalian β-catenin with p300 but not CBP[1].
Fz7-21S is a negative control of Fz7-21. Fz7-21 is a potent peptide antagonist of FZD7 receptors[1].
Wnt-C59 (C59) is a highly potent and oral porcupine (PORCN) inhibitor with an IC50 of 74 pM.
NCB-0846 is an orally available TNIK inhibitor with an IC50 of 21 nM.
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.
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].
BML-284 is selective and cell-permeable Wnt signaling activator.