Wnt Activator

CPA inhibitor (Compound 5) (Carboxypeptidase inhibitor) is an orally active competitive carboxypeptidase A (CPA) inhibitor with a K_i value of 0.32 μM. CPA inhibitor blocks the activity of carboxypeptidase A3 (CPA3). CPA activator activates the Wnt/Lrp6/β-catenin signaling pathway. CPA inhibitor reduces epithelial damage. CPA inhibitor is applicable to research related to inflammatory bowel disease, including ulcerative colitis and Crohn's disease.

L-Quebrachitol is a methoxy analog of inositol that can be isolated from plants. L-Quebrachitol has free-radical scavenging, gastroprotection, anti-platelet aggregation and anti-diabetic activity. L-Quebrachitol promotes osteoblastogenesis by uppregulation of BMP-2, runt-related transcription factor-2 (Runx2), MAPK (ERK, JNK, p38α), and Wnt/β-catenin signaling pathway.

GlcCer (d18:1/18:0) (C18 Glucosyl(β) ceramide (d18:1/18:0)) is a glycosphingolipids that activates the Wnt/β-catenin pathway by targeting LRP6. GlcCer (d18:1/18:0) drives EMT, migration, invasion and GBA1-mediated liver cancer metastasis. GlcCer (d18:1/18:0) accumulates to impair lysosomal function and induce toxic α-synuclein aggregation. GlcCer (d18:1/18:0) supports growth, sporulation, germination and virulence in Penicillium digitatum. GlcCer (d18:1/18:0) is reduced in demyelinated mouse corpus callosum. GlcCer (d18:1/18:0) can be used for the research of liver cancer, synucleinopathies, fungal, Parkinson’s disease and Gaucher disease.

Wnt/β-catenin agonist 2 is a potent Wnt agonist. Wnt/β-catenin agonist 2 activates Wnt/β-catenin signaling and can be used in the research of diseases related to the signal transduction. (From patent WO2007078113A1, compound 39)

Withanolide B is an active component of W. somnifera Dunal. Withanolide B promotes osteogenic differentiation of hBMSCs via ERK1/2 and Wnt/β-catenin signaling pathways. Withanolide B exhibits neuroprotective, anti-arthritic, anti-aging and anti-cancer effects.

Indirubin-3′-oxime (IDR3O), a synthetic derivative of indirubin, is a potent inhibitor of cyclin-dependent kinases (CDKs) and glycogen synthase kinase 3β (GSK3β). Indirubin-3′-oxime directly inhibits the activity of all three isoforms of JNK (JNK1, JNK2, and JNK3), with IC₅₀s of 0.8 μM, 1.4 μM, and 1.0 μM, respectively. Indirubin-3′-oxime can enhance height growth via activation of Wnt/β-catenin signaling in chondrocytes.

ARUK3001185 is a potent, selective, orally active and brain-penetrant inhibitor of Notum (IC₅₀ = 6.7 nM). ARUK3001185 can restore Wnt signaling in the presence of Notum in vitro. ARUK3001185 is selective against serine hydrolases, kinases, and drug targets. ARUK3001185 can be used to research the role of Notum plays in diseases.

Perfluoroundecanoic acid is a perfluoroalkyl substance (PFAS). Perfluoroundecanoic acid is an orally active oxidative stress inducer. Perfluoroundecanoic acid promotes macrophage M2 polarization, activates Wnt/β-catenin signaling and enhances β-catenin nuclear accumulation. Perfluoroundecanoic acid -induced M2 phenotype macrophage accelerates tumor progression in vitro and in vivo. Perfluoroundecanoic acid induces DNA damage, reproductive and pathophysiological dysfunctions via oxidative stress in male Swiss mice. Perfluoroundecanoic acid inhibits Leydig cell development in pubertal male rats via inducing oxidative stress and autophagy. Perfluoroundecanoic acid accelerates insulitis development in a mouse model of type 1 diabetes. Perfluoroundecanoic acid can be used for the study of ovarian cancer, type 1 diabetes and inflammation.

Dalosirvat (SM-04554) is a potent Wnt activator with an EC₅₀s of 28-29 nM. Dalosirvat can be used in the study of cancer.

Methyl vanillate, one of the ingredients in Oryza sativa Linn., is a Wnt/β-catenin pathway activator. A benzoate ester that is the methyl ester of vanillic acid. It has a role as an antioxidant and a plant metabolite.

Mirodenafil (SK3530) is an orally active, potent, reversible, and selective phosphodiesterase 5 (PDE5) inhibitor. Mirodenafil is a glucocorticoid receptor (GR) modulator Mirodenafil activates the Wnt/β-catenin signaling pathway by downregulating Dkk1 expression. Mirodenafil can be used for the research of erectile dysfunction (ED), Alzheimer’s disease (AD) and systemic sclerosis (SSc).

Wnt pathway activator 2 (compound 2) is a potent Wnt activator with an EC₅₀ of 13 nM.

Chrysosplenetin is an orally active polymethoxyflavone. Chrysosplenetin exerts anticancer effects by inhibiting topoisomerase, protecting DNA and inducing apoptosis. Chrysosplenetin acts as an antimalarial sensitizer, reverses Artemisinin (HY-B0094) resistance by inhibiting and downregulating P-glycoprotein, and enhances the efficacy of Artemisinin. Chrysosplenetin promotes bone formation by activating the Wnt/β-catenin pathway and exerts anti-osteoporotic effects.

Wnt/β-catenin agonist 3 (compound 98) is a Wnt/β-catenin signalling pathway agonist. Wnt/β-catenin agonist 3 can be used for the research of osteoporosis.

GSK3β-IN-2 (Compound S01) is the inhibitor for GSK3β with an IC₅₀ of 0.35 nM. GSK3β-IN-2 activates Wnt/β-catenin signaling pathway, promotes neurogenesis and neurite growth. GSK3β-IN-2 inhibits Aβ-induced tau hyperphosphorylation at Ser396, reduces the formation of neurofibrillary tangles. GSK3β-IN-2 ameliorates Alzheimer's Disease in zebrafish model.

Neurodazine is a neurogenic inducer, serve as a promoter of neurogenesisin pluripotent cells. Neurodazine promotes neurogenesis by activating Wnt and Shh signaling pathways..

WAY-362692 is a secreted frizzled-related protein (sFRP-1) inhibitor (IC₅₀ of 0.02 μM), targeting the netrin domain of sFRP-1. WAY-362692 can competitively inhibit the interaction between sFRP-1 and Wnt proteins, and activate the Wnt/β-catenin signaling pathway (EC₅₀ = 0.03 μM). WAY-362692 can activate osteoblasts and promote bone remodeling. WAY-362692 can be used for the research of metabolic disease, such as osteoporosis.

Arjunolic acid is an orally active, multifunctional bioactive compound. Arjunolic acid exhibits free radical scavenging activity, as well as fungal and bacterial activities. Arjunolic acid induces apoptosis (Apoptosis) in various cancer cells. Arjunolic acid protects hepatocytes against induced oxidative stress and apoptosis by reducing reactive oxygen species and inhibiting NF-κB activation. Arjunolic acid regulates pancreatic dysfunction in type 2 diabetic rats by blocking the activation of the TLR-4/MyD88 and canonical Wnt pathways. Arjunolic acid inhibits neuroinflammation and ameliorates depressive behaviors via the SIRT1/AMPK/Notch1 signaling pathway in microglia. Arjunolic acid improves Crohn's disease-like colitis by restoring gut microbiota composition and inhibiting TLR4 signaling. Arjunolic acid suppresses osteosarcoma progression by inhibiting Wnt3a-mediated M2 polarization of macrophages. Arjunolic acid ameliorates diabetic retinopathy via the autophagy pathway regulated by AMPK/mTOR/HO-1. Arjunolic acid is applicable to research related to type 2 diabetes, organ toxicity, depression, Crohn's disease, osteosarcoma, diabetic retinopathy, and testicular dysfunction.

Vitisin A ((+)-Vitisin A) is an orally active natural product with multiple pharmacological activities including anti-inflammatory, anti-tumor, anti-oxidant, anti-pathogenic microorganism, hypoglycemic and lipid-regulating, anti-osteoporotic, neuroprotective and cardiovascular protective effects. Vitisin A exhibits inhibitory effects on human AChE and MAO-B with IC₅₀ values of 1.29 µM and 4.94 µM, respectively. Vitisin A inhibits the ERK, MAPK, NF-κB, STAT1, HMGCR and TRAF6 pathways, downregulates the related phosphorylation and protein expression, while activates the Nrf2/HO-1 pathway and upregulates p21 expression. Vitisin A induces tumor cell apoptosis and cell cycle arrest, inhibits adipogenesis and lipid accumulation, while alleviates oxidative stress, suppresses inflammatory responses, blocks hepatic fibrosis, Cuproptosis and cholesterol synthesis, and increases the expression levels of central BDNF and TrkB. Vitisin A can be used in the research of tumors, infectious diseases, metabolic diseases, bone and joint diseases, liver diseases, skin injuries, as well as neurodegenerative and cognitive dysfunction-related diseases.

Nodakenetin is an orally active Wnt/β-catenin pathway activator. Nodakenetin reduces the level of DKK1, and upregulates c-Myc, cyclin D1 and survivin. Nodakenetin induces osteoprogenitor cell differentiation, upregulates bone formation biomarkers and prevents bone microstructure degeneration. Nodakenetin induces irritant skin reactions. Nodakenetin improves bone microstructure and histomorphometric parameters in osteoporotic mouse models. Nodakenetin can be used for osteoporosis-related research.