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
기타 Stem Cells & Wnt 억제제
아이소폼 선택적 제품
| Cat.No. | 제품명 | 정보 | 제품 사용 인용 | 제품 검증 |
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| S7086 | IWR-1-endo | IWR-1-endo (endo-IWR 1, IWR-1)는 Wnt3A를 발현하는 L-세포에서 IC50 180 nM을 나타내는 Wnt 경로 억제제이며, Axin-scaffolded 파괴 복합체를 안정화함으로써 Axin2 단백질 수준을 유도하고 β-catenin 인산화를 촉진합니다. |
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| S8968 | PRI-724 (Foscenvivint) | PRI-724 (Foscenvivint)은 β-catenin과 CBP의 상호작용을 방해하는 강력하고 특이적인 억제제입니다. |
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| S7085 | IWP-2 | IWP-2는 세포 없는 분석에서 27 nM의 IC50을 가진 Wnt 처리 및 분비 억제제이며, Porcn 매개 Wnt 팔미토일화의 선택적 차단제입니다. 이는 Wnt/beta-catenin에 일반적으로 영향을 미치지 않으며 Wnt 자극 세포 반응에 대해 아무런 영향을 나타내지 않습니다. IWP-2는 CK1δ를 특이적으로 억제합니다. |
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| S0733 | Tegatrabetan (BC-2059) | β-Catenin의 길항제인 Tegatrabetan (BC-2059, Tegavivint)은 β-catenin과 스캐폴드 단백질인 transducin β-like 1 (TBL1)의 결합 및 프로테아좀 분해를 방해하여 핵 내 β-catenin 수치를 감소시킵니다. |
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| S3842 | Isoquercitrin | Bidens bipinnata L에서 분리된 항암 활성을 가진 플라보노이드 화합물인 Isoquercitrin(Hirsutrin, 3-Glucosylquercetin, Quercetin 3-o-glucopyranoside)은 beta-catenin 핵 내 이동의 하류에서 작용하는 Wnt/beta-catenin 억제제입니다. |
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| S2662 | ICG-001 | ICG-001은 Wnt/β-catenin/TCF 매개 전사를 길항하며 3 μM의 IC50으로 CREB-binding protein(CBP)에 특이적으로 결합하지만, 관련 전사 보조 활성제인 p300과는 결합하지 않습니다. ICG-001은 apoptosis를 유도합니다. |
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| S1263 | CHIR-99021 (Laduviglusib) | Laduviglusib (CHIR-99021, CT99021)은 GSK-3α 및 GSK-3β 억제제로, IC50 값은 각각 10 nM 및 6.7 nM입니다. 이 화합물은 cyclin-dependent kinases(CDKs)에 대한 교차 반응성을 나타내지 않으며, CDKs 대비 GSK-3β에 대해 350배 높은 선택성을 보입니다. 이 화합물은 Wnt/beta-catenin 활성제로 기능하며 Autophagy를 유도합니다. |
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| S2924 | Laduviglusib (CHIR-99021) Hydrochloride | Laduviglusib (CHIR-99021; CT99021) HCl은 CHIR-99021의 염산염으로, 10 nM/6.7 nM의 IC50을 가진 GSK-3α/β 억제제입니다. CHIR-99021은 가장 유사한 동족체인 Cdc2 및 ERK2 대비 GSK-3에 대해 500배 이상의 선택성을 보입니다. CHIR-99021은 Wnt/beta-catenin 신호 전달 경로의 강력한 약리학적 활성제입니다. CHIR-99021은 빛에 의해 유도된 autophagy를 유의미하게 회복시키며 GR, RORα 및 autophagy 관련 단백질을 증강시킵니다. |
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| S1180 | XAV-939 | XAV-939(NVP-XAV939)은 Wnt/β-catenin 매개 전사를 세포 무함유 분석에서 11 nM/4 nM의 IC50으로 tankyrase1/2 억제를 통해 선택적으로 억제하며, axin 수준을 조절하고 CRE, NF-κB 또는 TGF-β에는 영향을 미치지 않습니다. |
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| S5992 | Heparan Sulfate | Heparan Sulfate(HS, Heparitin sulfate, Alpha-idosane, HHS 5, N-Acetylheparan Sulfate, Suleparoid, Tavidan)는 HS 프로테오글리칸(HSPGs)의 구성 요소로서, 세포 표면에 존재하는 선형 다당류입니다. Heparan Sulfate는 장 상피 세포(IECs)와 Wnt/beta-catenin 간의 결합 친화도에 영향을 미치며, 이를 통해 canonical Wnt 신호 전달의 활성화를 촉진하고 상피 손상 후 소장 음와(crypt)의 재생을 돕습니다. |
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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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