Wnt/beta-catenin Inhibitoren/Aktivatoren (Wnt/beta-catenin Inhibitors/Activators)

Weitere Stem Cells & Wnt Inhibitoren

• Ausgewählte Inhibitoren
• Inhibitoren (34)
• Modulatoren (3)
• Agonisten (4)
• Aktivatoren (11)
• Agonisten (4)

Kat.-Nr.	Produktname	Informationen	Publikationen	Validierung
S7086	IWR-1-endo	IWR-1-endo (endo-IWR 1, IWR-1) ist ein Wnt-Signalweginhibitor mit einer IC50 von 180 nM in Wnt3A-exprimierenden L-Zellen, induziert die Axin2-Proteinspiegel und fördert die β-Catenin-Phosphorylierung durch Stabilisierung von Axin-Gerüst-Destruktionskomplexen.	Nat Biotechnol, 2025, 10.1038/s41587-025-02833-3 Circulation, 2025, 151(20):1436-1448 Nat Commun, 2025, 16(1):5529
S8968	PRI-724 (Foscenvivint)	Foscenvivint (PRI-724) ist ein potenter und spezifischer Inhibitor, der die Interaktion von β-Catenin und CBP stört.	Cancer Discov, 2025, 10.1158/2159-8290.CD-25-0629 Cell Death Dis, 2025, 16(1):466 Biomed Pharmacother, 2025, 188:118225
S7085	IWP-2	IWP-2 ist ein Inhibitor der Wnt-Verarbeitung und -Sekretion mit einem IC50-Wert von 27 nM in einem zellfreien Assay, selektiver Blockierung der Porcn-vermittelten Wnt-Palmitoylierung, beeinflusst Wnt/β-catenin im Allgemeinen nicht und zeigt keine Wirkung gegen Wnt-stimulierte zelluläre Reaktionen. IWP-2 hemmt spezifisch CK1δ.	Sci Bull (Beijing), 2025, S2095-9273(25)00472-4 Nat Commun, 2025, 16(1):1999 Nat Commun, 2025, 16(1):4688
S0733	Tegatrabetan (BC-2059)	Tegatrabetan (BC-2059, Tegavivint), ein Antagonist von β-Catenin, stört die Bindung von β-Catenin an das Gerüstprotein Transducin-β-ähnliches 1 (TBL1) und den proteasomalen Abbau, was zu einer Abnahme der nukleären β-Catenin-Spiegel führt.	Nucleic Acids Res, 2024, 52(9):4950-4968 Cell Rep, 2024, 43(8):114532 J Transl Med, 2024, 22(1):201
S3842	Isoquercitrin	Isoquercitrin (Hirsutrin, 3-Glucosylquercetin, Quercetin 3-o-glucopyranosid), eine Flavonoidverbindung mit Antikrebsaktivität, isoliert aus Bidens bipinnata L, ist ein Inhibitor von Wnt/ A-Catenin, der nachgeschaltet der nukleären Translokation von A-Catenin wirkt.	Molecules, 2025, 30(6)1394 Commun Biol, 2023, 6(1):79 Front Pharmacol, 2023, 14:1290868
S2662	ICG-001	ICG-001 antagonisiert die Wnt/β-Catenin/TCF-vermittelte Transkription und bindet spezifisch an das CREB-bindende Protein (CBP) mit einem IC50 von 3 μM, jedoch nicht an den verwandten transkriptionellen Koaktivator p300. ICG-001 induziert Apoptose.	Cancer Discov, 2025, 10.1158/2159-8290.CD-25-0629 Adv Sci (Weinh), 2025, 12(40):e05702 Cell Rep Med, 2025, 6(2):101927
S1263	CHIR-99021 (Laduviglusib)	Laduviglusib (CHIR-99021, CT99021) ist ein GSK-3α- und GSK-3β-Inhibitor mit IC50-Werten von 10 nM bzw. 6,7 nM. Es zeigt keine Kreuzreaktivität gegen Cyclin-abhängige Kinasen (CDKs) und eine 350-fache Selektivität gegenüber GSK-3β im Vergleich zu CDKs. Diese Verbindung fungiert als Wnt/β-catenin-Aktivator und induziert Autophagy.	Cancer Cell, 2025, 43(4):776-796.e14 Circulation, 2025, 151(20):1436-1448 Nat Biomed Eng, 2025, 9(1):93-108
S2924	Laduviglusib (CHIR-99021) Hydrochloride	Laduviglusib (CHIR-99021; CT99021) HCl ist das Hydrochlorid von CHIR-99021, einem GSK-3α/β-Inhibitor mit einer IC50 von 10 nM/6,7 nM; CHIR-99021 zeigt eine über 500-fache Selektivität für GSK-3 im Vergleich zu seinen engsten Homologen Cdc2 und ERK2. CHIR-99021 ist ein potenter pharmakologischer Aktivator des Wnt/beta-Catenin-Signalwegs. CHIR-99021 rettet signifikant die lichtinduzierte Autophagy und erhöht GR, RORα und Autophagy-bezogene Proteine.	Cell, 2025, 188(11):2974-2991.e20 Cell, 2025, S0092-8674(25)00807-4 Protein Cell, 2025, pwaf098
S1180	XAV-939	XAV-939 (NVP-XAV939) hemmt selektiv die Wnt/β-catenin-vermittelte Transkription durch Tankyrase1/2-Hemmung mit einer IC50 von 11 nM/4 nM in zellfreien Assays, reguliert die Axin-Spiegel und beeinflusst CRE, NF-κB oder TGF-β nicht.	Nat Biotechnol, 2025, 10.1038/s41587-025-02649-1 Nat Cell Biol, 2025, 27(8):1240-1255 Nat Cell Biol, 2025, NONE
S5992	Heparan Sulfate	Heparan sulfate (HS, Heparitin sulfate, Alpha-idosane, HHS 5, N-Acetylheparan Sulfate, Suleparoid, Tavidan), ein Bestandteil von HS-Proteoglykanen (HSPGs), ist ein lineares Polysaccharid, das auf der Zelloberfläche vorhanden ist. Heparan sulfate beeinflusst die Bindungsaffinität von Darmepithelzellen (IECs) an Wnt, wodurch die Aktivierung der kanonischen Wnt-Signalübertragung gefördert und die Regeneration der Krypten des Dünndarms nach Epithelschäden erleichtert wird.	Mol Ther Methods Clin Dev, 2025, 33(1):101426 iScience, 2024, 27(6):110120 bioRxiv, 2024, 2024.05.23.595417
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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.