Wnt Inhibitor

ZY-444 is an anti-cancer agent, targeting pyruvate carboxylase (PC). ZY-444 suppresses the Wnt/β-catenin/Snail signaling pathway by blocking nuclear translocation of β-catenin. ZY-444 selectively inhibits proliferation, migration, and invasion and induces apoptosis in cancer cells. ZY-444 exhibits potent anti-tumor in cancer mouse models. ZY-444 can be used for the study of breast cancer, lung cancer (NSCLC), prostate cancer and iodine-refractory thyroid cancer.

xStAx-VHLL TFA is a β-catenin PROTAC degrader that promotes ubiquitination and proteasome degradation of β-catenin. xStAx-VHLL TFA inhibits the Wnt/β-catenin signaling pathway. xStAx-VHLL TFA can inhibit the proliferation of colon cancer cells and has anti-tumor activity.

CCT251545 is an orally bioavailable and potent inhibitor of WNT signaling with an IC₅₀ of 5 nM in 7dF3 cells. CCT251545 is a selective chemical probe for exploring the role of CDK8 and CDK19 in human disease.

KYA1797K is a potent and selective Wnt/β-catenin inhibitor with an IC₅₀ of 0.75 µM.

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.

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.

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.

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.

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.

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.

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.

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).

SGC-AAK1-1, a chemical probe, is a potent and selective AAK1 (AP2 associated kinase 1) inhibitor with an IC₅₀ of 270 nM and a K_i of 9 nM. SGC-AAK1-1 also potently inhibits BMP2K. SGC-AAK1-1 is used to study Wnt pathway related to AAK1.

2-Hydroxyanthraquinone is a product generated by the photochemical oxidation of Anthracene (ANT) (HY-Y0299). 2-Hydroxyanthraquinone induces ferroptosis in cardiomyocytes by depleting GSH and inhibiting GPX4, leading to cardiac developmental malformations. 2-Hydroxyanthraquinone causes damage to the cerebrovascular system and blood-brain barrier in zebrafish by downregulating the Wnt/β-catenin signaling pathway, as well as inducing inflammation and neuronal apoptosis. 2-Hydroxyanthraquinone can be used in studies related to cerebrovascular diseases and cardiotoxicity.

FzM1 is a negative allosteric modulator (NAM) of Frizzled receptor FZD4. FzM1 reduces WNT5A-dependent WNT responsive element (WRE) activity (log EC_50inh=?6.2). FzM1 binds to an allosteric binding site located in intracellular loop 3 (ICL3) of FZD4 and alters the conformation of the receptor, ultimately inhibiting the WNT/β-catenin cascade.

Miclxin (DS37262926) is a potent inhibitor of mutant β-catenin, involving in Wnt signaling pathway. Miclxin induces β-catenin-dependent apoptosis, leads to severe mitochondrial damage with the loss of mitochondrial membrane. Miclxin kills tumor via targeting to MIC60, a major components of the mitochondrial contact site and cristae organizing system (MICOS) complex.