Wnt Inhibitor

Raddeanin A is an oleanane-type triterpenoid saponin with oral activity. Raddeanin A inhibits SRC, mTOR, JNK, VEGFR2, NLRP3 inflammasome, Wnt/β-catenin, Wee1, PI3K/AKT signaling pathway, MAPK/ERK signaling pathway, AR-FL, AR-Vs, and downregulates the expression of p-PI3K and p-AKT. Raddeanin A inhibits osteoclast formation, bone resorption, osteolysis, cancer cell invasion, migration, proliferation, angiogenesis and epithelial-mesenchymal transition, while induces apoptosis, cell cycle arrest, ROS production, immunogenic cell death and dendritic cell maturation. Raddeanin A improves blood-retinal barrier function, alleviates inflammation, regulates the tumor microenvironment, and enhances the activity of anti-PD-1 antibody. Raddeanin A is applicable to the research of breast cancer-associated osteolysis, human osteosarcoma, colorectal cancer, glioblastoma, Alzheimer's disease, cholangiocarcinoma, melanoma, non-small cell lung cancer, castration-resistant prostate cancer and multiple myeloma.

Prinaberel (ERB-041) is a potent and selective estrogen receptor (ER) β agonist with IC₅₀s of 5.4, 3.1 and 3.7 nM for human, rat and mouse ERβ, respectively. Prinaberel displays >200-fold selectivity for ERβ over ERα. Prinaberel is a potent skin cancer chemopreventive agent that acts by dampening the WNT/β-catenin signaling pathway. Prinaberel induces ovarian cancer apoptosis.

Pamidronic acid, the second-generation nitrogen-containing bisphosphonate, is an inhibitor of bone loss. Pamidronic acid significantly inhibits subchondral bone loss in early osteoarthritis by upregulating the expression of OPG in cartilage and subchondral bone, and inhibiting the expression of RANKL and MMP-9 in both tissues, as well as TLR-4 in cartilage, thereby alleviating cartilage degeneration. Additionally, Pamidronic acid can inhibit the signaling of Wnt and β-catenin, and is applicable for research on osteoporosis and osteosarcoma.

KY-05009 is an ATP-competitive Traf2- and Nck-interacting kinase (TNIK) inhibitor with a K_i 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.

SSTC3 is a casein kinase 1α (CK1α) activator (K_d = 32 nM) that inhibits WNT signaling (EC₅₀ = 30 nM). SSTC3 exhibits minimal gastrointestinal toxicity compared to other classes of WNT inhibitors.

TK-129 is an orally active, low-toxicity, potent KDM5B inhibitor (with high affinity; IC₅₀=44 nM). TK-129 exerts cardioprotective effects by inhibiting KDM5B and blocking the KDM5B-associated Wnt pathway. TK-129 reduces ang II-induced activation of cardiac fibroblasts in vitro and reduces isoprenaline-induced myocardial remodelling and fibrosis in vivo. TK-129 can be used in studies of cardiovascular disease.

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.

M435-1279 is a UBE2T inhibitor. M435-1279 inhibits the Wnt/β-catenin signaling pathway hyperactivation through blocking UBE2T-mediated degradation of RACK1.

TFMB-(S)-2-HG is a potent TET2 inhibitor. TFMB-(S)-2-HG also inhibits the EglN prolyl hydroxylases. TFMB-(S)-2-HG downregulates Wnt3a, β-catenin (intranuclear) protein expression. TFMB-(S)-2-HG inhibits osteogenic differentiation of cells. TFMB-(S)-2-HG has the potential for the research of acute myeloid leukemia (AML).

Rosmantuzumab (OMP-131R10) is an anti-R-spondin 3 (RSPO3) humanized monoclonal antibody. Rosmantuzumab can be used for the research of advanced telapsed and refractory solid tumors.

QPH-FR is a LGR5 inhibitor. QPH-FR competitively binds to LGR5 and prevents the formation of the LGR5/RSPO1 complex. QPH-FR promotes RNF43/ZNRF3-mediated ubiquitination of FZD receptors, inhibits the Wnt β-catenin signaling pathway, and reduces the stemness of colorectal cancer cells. QPH-FR is applicable to relevant research on colorectal cancer.

Hematein is a oxidation product of hematoxylin acted as a dye. Hematein is an allosteric casein kinase II inhibitor with an IC₅₀ of 0.74 μM. Hematein inhibits Akt/PKB Ser129 phosphorylation, the Wnt/TCF pathway and increases apoptosis in lung cancer cells.

Pamidronate disodium (CGP 23339A), the second-generation nitrogen-containing bisphosphonate, is an inhibitor of bone loss. Pamidronate disodium significantly inhibits subchondral bone loss in early osteoarthritis by upregulating the expression of osteoprotegerin in cartilage and subchondral bone, and inhibiting the expression of RANKL and MMP-9 in both tissues, as well as TLR-4 in cartilage, thereby alleviating cartilage degeneration. Additionally, Pamidronate disodium can inhibit the signaling of Wnt and β-catenin, and is applicable for research on osteoporosis and osteosarcoma.

OM-153 is a potent and orally active tankyrase inhibitor with IC₅₀s of 13 nM and 2 nM for tankyrase 1 and tankyrase 2 (TNKS1/2), respectively. OM-153 inhibits luciferase-based Wnt/β-catenin signaling reporter activity with an IC₅₀ value of 0.63 nM. OM-153 shows inhibition of Wnt/β-catenin signaling and proliferation in COLO 320DM.

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).

Hexane-2,5-dione (2,5-HD) is an orally active, CNS-penetrant cytotoxic agent. Hexane-2,5-dione reduces BCL-2 and β-catenin/TCF transcriptional activity, increases BAX and active caspase-3 expression, and promotes apoptosis. Hexane-2,5-dione causes an accumulation of neurofilaments within axons in rats. Hexane-2,5-dione can be used for the research of neurodegenerative diseases.

Atranorin is a secondary metabolite of lichens and AKT inhibitor. Atranorin possesses multiple activities such as antibacterial, anti-inflammatory, antioxidant, anti-glycation, analgesic, and anti-tumor effects. Atranorin has IC₅₀ values for scavenging DPPH and ABTS free radicals of 117 μM and less than 10 μM, respectively. Additionally, Atranorin also exhibits effects in promoting wound healing. Atranorin can be used in the research of various diseases, including myelodysplastic syndromes, tumors, and inflammatory conditions.

aStAx-35R TFA, a stapled peptide, antagonizes nuclear form of β-catenin and inhibits Wnt signaling. aStAx-35R TFA inhibits competitively the binding of β-catenin to TCF4. aStAx-35R TFA selectively induces growth inhibition of Wnt-dependent cancer cells.

Dendrophenol (Moscatilin) is a NF-κB inhibitor that inhibits inflammation. Dendrophenol exerts potent cytotoxic effect against tumor cells and induces cell cycle arrest and apoptosis. Dendrophenol has antitumor activity. In addition, Dendrophenol can inhibit vascular calcification by inhibiting the activation of WNT3/β-catenin.

β-catenin-IN-3 (Compound C2) is a selective β-catenin inhibitor. β-catenin-IN-3 binds to allosteric site on the surface of β-catenin with K _D calculated at 54.96 nM. β-catenin-IN-3 selectively inhibits β-catenin via targeting a cryptic allosteric modulation site, lowers its cellular load. β-catenin-IN-3 significantly reduces viability of β-catenin driven cancer cells, and triggers β-catenin degradation via proteasome system in β-catenin-overexpressing cancer cells.