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]
Wnt/beta-catenin Inhibitors/Activators
Övrigt Stem Cells & Wnt Inhibitorer
- Utvalda inhibitorer
- Inhibitorer (34)
- Modulatorer (3)
- Agonister (4)
- Aktivatorer (11)
- Antagonister (4)
| Kat.nr. | Produktnamn | Information | Citeringar av produktanvändning | Produktvalideringar |
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| S7086 | IWR-1-endo | IWR-1-endo (endo-IWR 1, IWR-1) är en Wnt-vägshämmare med IC50 på 180 nM i L-celler som uttrycker Wnt3A, inducerar Axin2-proteinnivåer och främjar "-kateninfosforylering genom att stabilisera Axin-stöttade nedbrytningskomplex. |
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| S8968 | PRI-724 (Foscenvivint) | Foscenvivint (PRI-724) är en potent och specifik hämmare som bryter interaktionen mellan β-catenin och CBP. |
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| S7085 | IWP-2 | IWP-2 är en inhibitor av Wnt-bearbetning och sekretion med IC50 på 27 nM i en cellfri analys, selektiv blockering av Porcn-medierad Wnt-palmitoylering, påverkar inte Wnt/β-catenin i allmänhet och visar ingen effekt mot Wnt-stimulerade cellulära svar. IWP-2 hämmar specifikt CK1δ. |
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| S0733 | Tegatrabetan (BC-2059) | Tegatrabetan (BC-2059, Tegavivint), en antagonist av β-Catenin, stör bindningen av β-catenin med scaffold-proteinet transducin β-like 1 (TBL1) och proteasomal nedbrytning, vilket leder till minskningar av de nukleära nivåerna av β-catenin. |
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| S3842 | Isoquercitrin | Isoquercitrin (Hirsutrin, 3-Glucosylquercetin, Quercetin 3-o-glucopyranoside), en flavonoidförening med anti-canceraktivitet isolerad från Bidens bipinnata L, är en hämmare av Wnt/β-catenin som verkar nedströms om β-catenin-nukleär translokation. |
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| S2662 | ICG-001 | ICG-001 motverkar Wnt/β-catenin/TCF-medierad transkription och binder specifikt till CREB-bindande protein (CBP) med IC50 på 3 μM, men är inte den relaterade transkriptionella koaktivatorn p300. ICG-001 inducerar apoptos. |
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| S1263 | CHIR-99021 (Laduviglusib) | Laduviglusib (CHIR-99021, CT99021) är en GSK-3α- och GSK-3β-hämmare med IC50-värden på 10 nM respektive 6,7 nM. Den uppvisar ingen korsreaktivitet mot cyklinberoende kinaser (CDK) och visar en 350-faldig selektivitet mot GSK-3β jämfört med CDK. Denna förening fungerar som en Wnt/β-catenin-aktivator och inducerar autophagy. |
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| S2924 | Laduviglusib (CHIR-99021) Hydrochloride | Laduviglusib (CHIR-99021; CT99021) HCl är hydroklorid av CHIR-99021, som är en GSK-3α/β-hämmare med IC50 på 10 nM/6,7 nM; CHIR-99021 visar större än 500-faldig selektivitet för GSK-3 jämfört med dess närmaste homologer Cdc2 och ERK2. CHIR-99021 är en potent farmakologisk aktivator av signalvägen Wnt/beta-catenin. CHIR-99021 räddar signifikant ljusinducerad autophagy och förstärker GR, RORα och autofagi-relaterade proteiner. |
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| S1180 | XAV-939 | XAV-939 (NVP-XAV939) hämmar selektivt Wnt/β-catenin-medierad transkription genom tankyrase1/2-hämning med IC50 på 11 nM/4 nM i cellfria analyser, reglerar axinnivåer och påverkar inte CRE, NF-κB eller TGF-β. |
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| S5992 | Heparan Sulfate | Heparan Sulfate (HS, Heparitin sulfat, Alfa-idosan, HHS 5, N-Acetylheparan Sulfate, Suleparoid, Tavidan), en beståndsdel i HS-proteoglykaner (HSPG), är en linjär polysackarid som finns på cellytan. Heparan Sulfate påverkar bindningsaffiniteten hos tarmepitelceller (IEC) till Wnt, vilket främjar aktivering av kanonisk Wnt-signalering och underlättar regenerering av tunntarmskryptor efter epitelial skada. |
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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.
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