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Wnt/beta-catenin inhibitors/activators

Wnt proteins form a family of highly conserved secreted signaling molecules that regulate cell-to-cell interactions during embryogenesis. Wnt signalling pathway plays a key role in the development of CSC(Cancer stem cell) and it may be a significant step in the development of a large number of tomours. As currently understood, Wnt proteins bind to receptors of the Frizzled and LRP families on the cell surface.  [show the full text]

Other Stem Cells & Wnt Related Inhibitors

OCT Stemness kinase PORCN Fascin SFRP

Isoform-selective Products

Cat.No. Product Name Information Product Use Citations Product Validations
S2662 ICG-001 ICG-001 antagonizes Wnt/β-catenin/TCF-mediated transcription and specifically binds to CREB-binding protein (CBP) with IC50 of 3 μM, but is not the related transcriptional coactivator p300. ICG-001 induces apoptosis.
Cancer Discov, 2025, 10.1158/2159-8290.CD-25-0629
Adv Sci (Weinh), 2025, 12(40):e05702
Cell Rep Med, 2025, 6(2):101927
Verified customer review of ICG-001
S7086 IWR-1-endo IWR-1-endo (endo-IWR 1, IWR-1) is a Wnt pathway inhibitor with IC50 of 180 nM in L-cells expressing Wnt3A, induces Axin2 protein levels and promotes β-catenin phosphorylation by stabilizing Axin-scaffolded destruction complexes.
Nat Biotechnol, 2025, 10.1038/s41587-025-02833-3
Circulation, 2025, 151(20):1436-1448
Circulation, 2025, 151(20):1436-1448
Verified customer review of IWR-1-endo
S7085 IWP-2 IWP-2 is an inhibitor of Wnt processing and secretion with IC50 of 27 nM in a cell-free assay, selective blockage of Porcn-mediated Wnt palmitoylation, does not affect Wnt/β-catenin in general and displays no effect against Wnt-stimulated cellular responses. IWP-2 specifically inhibits CK1δ.
Sci Bull (Beijing), 2025, S2095-9273(25)00472-4
Nat Commun, 2025, 16(1):1999
Nat Commun, 2025, 16(1):4688
Verified customer review of IWP-2
S8968 PRI-724 (Foscenvivint) Foscenvivint (PRI-724) is a potent and specific inhibitor that disrupts the interaction of β-catenin and CBP.
Cancer Discov, 2025, 10.1158/2159-8290.CD-25-0629
Cell Death Dis, 2025, 16(1):466
Biomed Pharmacother, 2025, 188:118225
S3842 Isoquercitrin Isoquercitrin (Hirsutrin, 3-Glucosylquercetin, Quercetin 3-o-glucopyranoside), a flavonoid compound with anticancer activity isolated from Bidens bipinnata L, is an inhibitor of Wnt/β-catenin that acts downstream of the β-catenin nuclear translocation.
Molecules, 2025, 30(6)1394
Commun Biol, 2023, 6(1):79
Front Pharmacol, 2023, 14:1290868
S0733 Tegatrabetan (BC-2059) Tegatrabetan (BC-2059, Tegavivint), an antagonist of β-Catenin, disrupts the binding of β-catenin with the scaffold protein transducin β-like 1 (TBL1) and proteasomal degradation, leading to declines in the nuclear levels of β-catenin.
Nucleic Acids Res, 2024, 52(9):4950-4968
Cell Rep, 2024, 43(8):114532
J Transl Med, 2024, 22(1):201
S1263 CHIR-99021 (Laduviglusib) Laduviglusib (CHIR-99021, CT99021) is a GSK-3α and GSK-3β inhibitor with IC50 values of 10 nM and 6.7 nM, respectively. It does not exhibit cross-reactivity against cyclin-dependent kinases (CDKs) and shows a 350-fold selectivity toward GSK-3β compared to CDKs. This compound functions as a Wnt/β-catenin activator and induces autophagy.
Cancer Cell, 2025, 43(4):776-796.e14
Circulation, 2025, 151(20):1436-1448
Circulation, 2025, 151(20):1436-1448
Verified customer review of CHIR-99021 (Laduviglusib)
S2924 Laduviglusib (CHIR-99021) Hydrochloride Laduviglusib (CHIR-99021; CT99021) HCl is hydrochloride of CHIR-99021, which is a GSK-3α/β inhibitor with IC50 of 10 nM/6.7 nM; CHIR-99021 shows greater than 500-fold selectivity for GSK-3 versus its closest homologs Cdc2 and ERK2. CHIR-99021 is a potent pharmacological activators of the Wnt/beta-catenin signaling pathway. CHIR-99021 significantly rescues light-induced autophagy and augments GR, RORα and autophagy-related proteins.
Cell, 2025, 188(11):2974-2991.e20
Cell, 2025, S0092-8674(25)00807-4
Protein Cell, 2025, pwaf098
Verified customer review of Laduviglusib (CHIR-99021) Hydrochloride
S1180 XAV-939 XAV-939 (NVP-XAV939) selectively inhibits Wnt/β-catenin-mediated transcription through tankyrase1/2 inhibition with IC50 of 11 nM/4 nM in cell-free assays, regulates axin levels and does not affect CRE, NF-κB or TGF-β.
Nat Biotechnol, 2025, 10.1038/s41587-025-02649-1
Nat Cell Biol, 2025, 27(8):1240-1255
Nat Cell Biol, 2025, NONE
Verified customer review of XAV-939
S5992 Heparan Sulfate Heparan sulfate (HS, Heparitin sulfate, Alpha-idosane, HHS 5, N-Acetylheparan Sulfate, Suleparoid, Tavidan), a constituent of HS proteoglycans (HSPGs), is a linear polysaccharide present on the cell surface. Heparan sulfate influences the binding affinity of intestinal epithelium cells (IECs) to Wnt, thereby promoting activation of canonical Wnt signaling and facilitating regeneration of small intestinal crypts after epithelial injury.
Mol Ther Methods Clin Dev, 2025, 33(1):101426
iScience, 2024, 27(6):110120
bioRxiv, 2024, 2024.05.23.595417
S7914 ISX-9 (Isoxazole 9) Isoxazole 9 (Isx-9) is a synthetic promotor of adult neurogenesis by triggering neuronal differentiation of adult neural stem/precursor cells (NSPCs). Isoxazole 9 (Isx-9) activates multiple pathways including TGF-β induced epithelial–mesenchymal transition (EMT) signaling, canonical and non-canonical Wnt signaling at different stages of cardiac differentiation.
iScience, 2025, 28(3):112015
Front Cell Dev Biol, 2025, 13:1513163
Cell Regen, 2025, 14(1):18

Signaling Pathway Map

The Wnt/β-catenin signalling pathway is an important mechanism of study for researchers of human diseases as it plays a role in oncology when overactivated, however, reduced signalling of this pathway also results in abnormal bone development and neurodegenerative illnesses. Depending on the indication of use, development of inhibitors or activators of the Wnt/β-catenin signalling pathway is an important area of focus.

Normally, regulation of the Wnt/β-catenin signalling pathway occurs by a large protein assembly called the β-catenin destruction complex that maintains low concentrations of β-catenin in the cytoplasm, and consequently in the nucleus. The β-catenin destruction complex is comprised of glycogen synthase kinase 3 (GSK3α/ GSK3β), casein kinase Iα (CKIα), Axin1/Axin2 scaffolding, and adenomatous polyposis coli (APC) – a tumor suppressor protein. Recruitment of β-catenin to the destruction complex leads to the phosphorylation of β-catenin N-terminus residues by CKIα and GSK3, following which ubiquitination and degradation events occur.  Sequestering β-catenin at several N-terminal serine and threonine residues to the β-catenin destruction complex are Axin and APC. Similarly, it is believed these constituents of the β-catenin destruction complex regulate β-catenin efflux from the nucleus. The low concentration of β-catenin in the cell restricts β-catenin to the essential role of cadherin-mediated cell adhesion.  An additional mechanism controlling the expression of Wnt signalling in the cell involves the inhibition of Wnt specific gene transcription by the T-cell factor (TCF) family of proteins.[1]

Activation of the Wnt/β-catenin signalling pathway is signified by the formation of a “Wnt signalosome” – a large protein complex that develops following the recognition of Wnt protein on the cell surface by a set of proteins called the seven-pass transmembrane Frizzled (Fz) family and its co-receptor, low density lipoprotein receptor related protein (LRP5/LRP6).ii The Wnt signalosome inhibits the activity of the β-catenin destruction complex by recruiting several components of the destruction complex to the membrane. As a consequence, the buildup of β-catenin’s unphosphorylated form results in the cytoplasm and subsequently in the nucleus. It is in the nucleus where rising concentrations of β-catenin combine with TCF proteins to transform this protein from an inhibitory protein to an activator of Wnt-signalling pathway by encouraging the transcription of the Wnt-responsive gene.[1]

Among cancer research, Wnt/β-catenin signalling is an area of focus since loss-of-function mutations in the APC gene results in β-catenin stabilization. Deletions within a chromosomal region containing the APC gene is understood to be associated with a hereditary disease known as familial adenomatous polyposis that yield intestinal polyps in large numbers that ultimately gives rise to tumors. Alternatively, mutations that promote gain-of-function of the APC gene inhibit the β-catenin destruction complex from limiting β-catenin concentrations in the cell. Additionally, some cancers have been correlated to a loss of Axin1 or Axin2 function. Overexpression of the Wnt/ β-catenin signalling pathway results in the constitutive activation of c-myc, and is most commonly linked to colorectal cancer.[2]

Since the Wnt/β-catenin signalling pathway plays a critical role in cancer, clinical research has yielded several new targets that may positively influence Wnt/β-catenin signalling where its absence is related to disease. Potential new drug targets include two lipid kinases that were found with the accumulation of β-catenin among HEK293T cells transfected with short inhibitory RNAs (siRNAs) targeting human kinases, these include: (1) phosphatidylinositol 4-kinase type IIα (PI4KIIα), and (2) phosphatidylinositol-4-phosphate 5-kinase type Iβ (PIP5Kiβ). Additionally, three human homologs of Drosophila PAR-1 can also provide useful drug targets as these elements activate Wnt/β-catenin signalling pathway as well.[2]

There are many enzymes involved in the Wnt/β-catenin signalling pathway and knowing whether activation or repression is best suited will determine the molecular strategy to explore for therapeutic benefit.