β-catenin-in-2

β-catenin-IN-2, a potent inhibitor of β-catenin, is suitable for use in colorectal cancer research.

PTK7/β-catenin-IN-2 (compound 04967) acts as an inhibitor targeting both PTK7 and β-catenin, effectively preventing their interaction with an IC 50 of 5.6 μM and disrupting the Wnt/β-catenin signaling pathway. This interference supports its role in inhibiting cell growth reliant on Wnt signaling, exhibiting anticancer capabilities. Additionally, the compound displays an inhibitory effect on the binding of p53 to MDM2, with an IC 50 value of 157.1 μM [1].

Wnt/β-catenin-IN-2 (Compound 3235-0367) serves as an inhibitor of the Wnt/β-catenin signaling pathway, exhibiting IC50 and KD values of 7.1 and 2.5 μM, respectively. It is applicable in cancer research [1].

TNIK-IN-2 is an inhibitor Traf2- and Nck-interacting protein kinase (TNIK, IC50 = 1.33 μM)) which is a downstream signal protein of the Wnt/β-catenin pathway.

1. Isoquercetin (3-Glucosylquercetin) is a potential stimulator of bone mineralization used for prophylaxis of osteoporotic disorders. 2. Isoquercetin may be as a potential therapeutic agent against neurodegeneration in Parkinson's disease. 3. Isoquercetin is an inhibitor of Wnt/β-catenin and may be as a potential novel anti-tumoral agent, such as against human pancreati,liver cancer related to opioid receptors and to the activation of the mitogen-activated protein kinase (MAPK) signalling pathway. .

Bisdemethoxycurcumin (Curcumin III) is a natural demethoxy derivative of curcumin. It is a potent activator of macrophage phagocytosis, interacting with 1α, 25-dihydroxy vitamin D3 to stimulate amyloid-β clearance by macrophages (optimal stimulation at 100 nM BDMC) [1]. More stable than curcumin in physiological media, BDMC suppresses proliferation of cancer cells [2]. It down-regulates the transcriptional coactivator p300, suppressing the Wnt/β-catenin pathway, and inhibits LPS induction of iNOS expression [3].

TNKS-2-IN-1 is a TNKS-2 inhibitor.TNKS-2-IN-1 inhibits TNKS-1 and TNKS-2 with IC50s of 259 nM and 1100 nM, respectively.TNKS-2-IN-1 has antimicrobial activity against E. coli and S. aureus.TNKS-2-IN-1 inhibits the release of IL-1β from the NLRP3 inflammasome (IC50: 5 μM) by inhibiting IL-1β release from ATP-stimulated J1A.774 cells.

FMF-04-159-2 is a potent covalent cell cycle protein-dependent kinase 14 (CDK14) inhibitor with IC₅₀ of 39.6 nM for CDK14 and 256 nM for CDK2.FMF-04-159-2 is able to reduce α-synuclein (α-Syn ) aggregation in neurons and plays a role in Parkinson's disease models, and also inhibits triple-negative breast cancer (TNBC) progression and metastasis by attenuating Wnt/β-catenin signaling.

Tankyrase-IN-2 is a selective, potent and orally active inhibitor of tankyrase with IC50s of 10, 7, and 710 nM for TNKS1, TNKS2 as well as PARP1, respectively

LZZ-02 inhibits the transcriptional activity of β-catenin by stabilizing axin 2 and reducing the levels of downstream proteins, including c-Myc and cyclin D1, which leads to the degradation of β-catenin. This results in the effective reduction of tumor xenografts derived from colon cell lines.

GSK-3β inhibitor24 (Compound 41) is a potent GSK-3β inhibitor with an IC50 of 0.22 nM. It increases GSK-3β phosphorylation at the Ser9 site in a dose-dependent manner and inhibits tau protein hyperphosphorylation by reducing the abundance of p-tau-Ser396. The compound upregulates β-catenin and neurogenesis-related markers (GAP43 and MAP-2), demonstrating significant anti-Alzheimer's disease (AD) activity.

Cardionogen-2 is a biphasic cardiac regulatory agent that can either promote or inhibit heart formation depending on the intervention stage. It inhibits Wnt/β-catenin-dependent transcription in mouse embryonic stem cells and zebrafish embryos.

TCF4/β-catenin-IN-1 (Compound 8b) is an inhibitor of TCF4/β-catenin that induces apoptosis. This compound enhances the expression of p53, caspase-3, caspase-8, caspase-9, and Bax proteins, while reducing Bcl-2 protein levels. TCF4/β-catenin-IN-1 also inhibits CYP3A4, CYP1A2, and CYP2C19, demonstrating significant cytotoxic activity in cancer cells.

GSK3β-IN-2 (Compound S01) is an inhibitor of GSK3β with an IC50 of 0.35 nM. It activates the Wnt/β-catenin signaling pathway, promoting neurogenesis and neurite outgrowth. GSK3β-IN-2 reduces tau protein phosphorylation induced by Aβ at the Ser396 site, thereby decreasing neurofibrillary tangles. Furthermore, GSK3β-IN-2 improves Alzheimer's disease symptoms in a zebrafish model.

S118 is an orally active inhibitor of the sphingosine-1-phosphate receptor 2 (S1P2 receptor). It prevents the binding of the S1P2 receptor to dapper1 (Dpr1), reduces the accumulation of β-catenin, and blocks the nuclear translocation of the S1P2 receptor. This process inhibits inflammation, fibrosis, and epithelial-mesenchymal transition (EMT), thereby exhibiting anti-idiopathic pulmonary fibrosis (IPF) activity. S118 is considered promising for research in idiopathic pulmonary fibrosis.

TNKS-2-IN-3 (Compound 5) is a selective and competitive inhibitor of Tankyrase 2 (TNKS2), with an IC50 value of 0.3 nM. It exhibits over 20-fold selectivity for TNKS2 compared to TNKS1 and more than 100-fold selectivity over PARP1/2. By inhibiting TNKS2-mediated ADP ribosylation, TNKS-2-IN-3 stabilizes axin and suppresses the Wnt/β-catenin pathway, demonstrating antiproliferative activity in colorectal cancer cells. TNKS-2-IN-3 holds potential for research in solid tumors with aberrant Wnt pathway activation, such as colorectal cancer.

XRF-1021 is an orally active HIPK2 inhibitor with an IC50 value of 0.18 μM. It reduces the expression of fibrosis markers such as fibronectin, type I collagen, and α-SMA in NRK-49F and HK-2 cells stimulated by TGF-β1. XRF-1021 blocks signaling pathways including TGF-β, NF-κB, p53, Wnt/β-catenin, and Notch. Additionally, it alleviates renal injury and fibrosis in vivo and can be utilized for research in chronic kidney disease.

CHIR-99021 HCl (Laduviglusib HCl) is a highly potent and selective inhibitor of GSK-3α/β, with IC50 values of 10 nM and 6.7 nM respectively. It demonstrates remarkable selectivity for GSK-3, with over 500-fold selectivity over CDC2, ERK2, and other protein kinases. Additionally, CHIR-99021 HCl serves as a robust activator of the Wnt/β-catenin signaling pathway. Moreover, it exhibits the ability to enhance self-renewal in both mouse and human embryonic stem cells. Furthermore, CHIR-99021 HCl induces autophagy [1] [2] [3].

YW1128 is an inhibitor of Wnt/β-catenin signaling with an IC50 value of 4.1 nM in a reporter assay.1 It decreases protein levels of β-catenin in the presence of the GSK3β inhibitor lithium chloride and increases protein levels of Axin1 in HEK293 cells. YW1128 decreases lipid accumulation and the expression of gluconeogenic and lipogenic genes in Huh7 cells. It decreases the hepatic expression of Wnt target genes, improves glucose tolerance, and prevents body weight increases and hepatic lipid accumulation in mice fed a high-fat diet, but not mice fed normal chow, when administered at a dose of 40 mg/kg every other day for 11 weeks.References1. Obianom, O.N., Ai, Y., Li, Y., et al. Triazole-based inhibitors of the Wnt/β-catenin signaling pathway improve glucose and lipid metabolism in diet-induced obese mice. J. Med. Chem. 62(2), 727-741 (2019). YW1128 is an inhibitor of Wnt/β-catenin signaling with an IC50 value of 4.1 nM in a reporter assay.1 It decreases protein levels of β-catenin in the presence of the GSK3β inhibitor lithium chloride and increases protein levels of Axin1 in HEK293 cells. YW1128 decreases lipid accumulation and the expression of gluconeogenic and lipogenic genes in Huh7 cells. It decreases the hepatic expression of Wnt target genes, improves glucose tolerance, and prevents body weight increases and hepatic lipid accumulation in mice fed a high-fat diet, but not mice fed normal chow, when administered at a dose of 40 mg/kg every other day for 11 weeks. References1. Obianom, O.N., Ai, Y., Li, Y., et al. Triazole-based inhibitors of the Wnt/β-catenin signaling pathway improve glucose and lipid metabolism in diet-induced obese mice. J. Med. Chem. 62(2), 727-741 (2019).

Pentagalloylglucose (Penta-O-galloyl-β-D-glucose) is a natural product functioning as an apoptosis and autophagy inducer. Possessing oral bioavailability, this compound exhibits diverse pharmacological effects including antiviral and antitumor activities through modulation of the GSK3β/β-catenin and p53 signaling pathways.

Wnt/β-catenin agonist 2 activates Wnt/β-catenin signaling and is an effective Wnt agonist. Wnt/β-catenin agonist 2 can be used in the study of diseases related to signal transduction and is closely related to cancer invasion and metastasis.

1. Kirenol (Kirel) has anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities. 2. Kirenol is effective against gram-positive bacteria. 3. Kirenol possesses antitumor action on human chronic myeloid leukemia K562 cells in vitro. 4. Kirenol is capable of promoting osteoblast differentiation in MC3T3-E1 cells through activation of the BMP and Wnt/β-catenin signaling pathways. 5. Kirenol treatment reduces pro-inflammatory cytokine secretion, increases anti-inflammatory cytokine production, inhibits cell proliferation and induces apoptosis of CII-specific lymphocytes in vitro.

Wnt signaling is required for direct multiple biological processes and also plays key roles in the pathogenesis of various diseases. Cyclic AMP response element-binding protein (CREB) is a transcription factor that is a member of the leucine zipper family of DNA binding proteins. This protein binds as a homodimer to the cAMP-responsive element, an octameric palindrome. The protein is phosphorylated by several protein kinases, and induces transcription of genes in response to hormonal stimulation of the cAMP pathway. Via generating a transcriptionally active complex with β-catenin, CREB acts as a mediator of Wnt signaling.ICG-001 is an inhibitor of β-catenin/CREB mediated transcription. The direct cellular target of ICG-001 is CREB. the inhibitory IC50of ICG-001 against β-catenin/CREB mediated transcription was 3 μM. ICG-001 treatment at the concentration of 25 μM for 24h significantly increased caspase activity in both colon cancer cell lines SW480 and HCT116 cell lines but not in normal colonic epithelial cells CCD-841Co. In a cell growth inhibition assay, the IC50s of ICG-001 against SW480 and HCT116 cells were 4.43 μM and 5.95 μM, respectively.In a SW620 nude mouse xenograft model, an water-soluble analog of ICG-001 given at the dose of 150 mg/kg i.v. once in every 2 days dramatically suppressed tumor growth. In a bleomycin-induced pulmonary fibrosis mice model, ICG-001 given at the dose of 5 mg/kg per day reversed pulmonary fibrosis. In a rat myocardial infarction model, ICG-001 was administrated subcutaneously at the dose of 50 mg/kg/day for 10 days which significantly improved cardiac contractile function after myocardial infarction in the rats.

Carboxylesterase-IN-2 is a potent Carboxylesterase Notum inhibitor (IC50 <= 10 nM).Carboxylesterase-IN-2 has potential for the study of cancer diseases.