Wnt/beta-catenin

CHIR-99021 (CT99021) is an activator of the Wnt β-catenin signaling pathway and a GSK-3α β inhibitor (IC50=10 6.7 nM) with selective and oral activity.CHIR-99021 induces cellular autophagy, which enhances self-renewal in mouse and human embryonic stem cells.

ICG001 is a β-catenin TCF-mediated transcription inhibitor that selectively blocks β-catenin CBP interaction without interfering with β-catenin p300 interaction. It specifically binds to CREB protein with an IC50 of 3 μM.

XAV-939 (NVP-XAV939) is a Tankyrase (TNKS) inhibitor that inhibits TNKS1 and TNKS2 (IC50=11 4 nM). XAV-939 selectively inhibits Wnt β-catenin-mediated transcription.

Heparan sulfate is a natural product, a linear polysaccharide. Heparan sulfate occurs as a proteoglycan (HSPG) that is tightly attached to cell surface or extracellular matrix proteins.

1. Ginkgetin has anti-influenza virus and anti-fungal activities. 2. Ginkgetin has anti-inflammatory activity, can down-regulates COX-2 induction in vivo against skin inflammatory responses. 3. Ginkgetin is a good STAT3 inhibitor and may be a useful lead

Salinomycin (Procoxacin), a polyether potassium ionophore antibiotic, specifically inhibits the growth of gram-positive bacteria, acts as a potent inhibitor of Wnt β-catenin signaling by blocking Wnt-induced LRP6 phosphorylation, and demonstrates selective activity against human cancer stem cells.

Laduviglusib trihydrochloride (CT99021 trihydrochloride) is a selective glycogen synthase kinase 3 (GSK-3) inhibitor with IC50s of 10 nM and 6.7 nM for GSK-3α and GSK-3β. Laduviglusib trihydrochloride inhibits human GSK-3β with a Ki of 9.8 nM. Laduviglusib trihydrochloride is an activator of Wnt β-catenin signaling. Laduviglusib trihydrochloride induces autophagy.

SRI 37892 is a Fzd7 inhibitor with potent activities against Wnt β-catenin signaling and cancer cell viability.

Gossypolone is is a proposed major metabolite of gossypol. Gossypolone reduces Notch Wnt signaling and induces apoptosis.

Romosozumab (AMG-785) is a humanized monoclonal antibody that binds and inhibits sclerostin, increasing bone formation and decreasing bone resorption.Romosozumab is used in the study of postmenopausal osteoporosis.

IWR-1 (IWR-1-endo), a Wnt pathway inhibitor, stabilizes the Axin destruction complex(EC50=0.2 uM).

1. Xanthatin has cytotoxic activity. 2. Xanthatin has antibacterial and antifungal activies against MRSA. 3. Xanthatin may have therapeutic potential against NSCLC. 4. Xanthatin can inhibit murine melanoma B16-F1 cell proliferation possibly associated wit

MSAB is a selective inhibitor of Wnt β-catenin signaling. MSAB binds to β-catenin, promoting its degradation, and specifically downregulates Wnt β-catenin target genes.

1. Triptonide (PG 492) is effective in the treatment of autoimmune diseases and has potent antileukemic and antitumor activities. 2. Triptonide possesses anti-inflammatory activity, upregulate the expression of IL-37, and this expression was suppressed by ERK1 2 and p38 MAPK inhibitors.

PRI-724 is a second-generation, selective small molecule inhibitor of the β-catenin CBP interaction.

Toxoflavin (Xanthothricin) is an antagonist of the transcription factor 4 (TCF4) β-catenin complex and also inhibits KDM4A.

Echinacoside is a natural polyphenolic compound with various kinds of pharmacological activities, such as anti-inflammatory, antioxidative, hepatoprotective, neuroprotective, nitric oxide radical-scavenging and vasodilative ones.

SKL2001, an agonist of the Wnt β-catenin pathway, can disrupt the Axin β-catenin interaction.

Wnt-C59 (C59) is a highly effective and specific Wnt signaling antagonis with PORCN enzymatic activity.

IWP-2 is a Wnt pathway inhibitor (IC50=27 nM) and an ATP-competitive CK1δ inhibitor (IC50=40 nM for M82FCK1δ). IWP-2 inhibits self-renewal of embryonic stem cells and has been used in stem cell and organoid research.

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].

ZW4864 (free base) is an orally active and selective β-catenin B-Cell lymphoma 9 protein-protein interaction (β-catenin BCL9 PPI) inhibitor, with a K_i value of 0.76 μM and an IC_50 value of 0.87 μM [1]. ZW4864 (free base) also demonstrates good pharmacokinetic properties.

ABC99 is a selective irreversible inhibitor of the wnt-deacylating enzyme. ABC99 inhibited NOTUM (IC50: 13 nM). It also showed excellent selectivity across the serine hydrolase family.

C-82 is a specific CBP β-catenin antagonist. It inhibits the binding between β-catenin and CBP and increases the binding between β-catenin and p300.

Trachelogenin ((-)-Trachelogenin), isolated from Combretum fruticosum, is an HCV entry inhibitor with anti-proliferative effects. Its mechanism is related to affecting the phosphorylation of key proteins such as β-Catenin, c-Myc and GSK3 in the β-Catenin signaling pathway. chemical and concentration-dependent. Trachelogenin has antiviral, anti-inflammatory and analgesic activities with IC50 of 0.325 and 0.259 μg mL in HCVcc and HCVpp models, respectively.

Wogonin (Vogonin) is a cell-permeable and orally available flavonoid that displays anti-inflammatory and anticancer properties.

Adavivint (SM04690) is a selective inhibitor of the typical Wnt signaling pathway. In SW480 cells, EC50=19.5 nM was measured using high-throughput TCF LEF reporter gene experiments.

DK419 is an orally active inhibitor of Wnt β-catenin signaling, with an IC50 of 0.19 μM. DK419 decreases protein lelvels of Axin2, β-catenin, c-Myc, Cyclin D1 and Survivin.It also induces production of pAMPK.

ICG001 antagonizes Wnt β-catenin TCF-mediated transcription and specifically binds to element-binding protein (CREB)-binding protein (CBP) with IC50 of 3 μM, but is not the related transcriptional coactivator p300.

NRX-252114 (NRX252114) induces degradation of mutant β-catenin NRX-252114 is a potent enhancer of the interaction of β-catenin with the homologous E3 ligase SCFβ-TrCP, and is able to enhance the binding of pSer33 S37A β-catenin to β-TrCP with an EC50 of 6.5 nM and a Kd of 0.4 nM. Kd is 0.4 nM.

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. .

ISX-9 (Isoxazole 9) is essential for activating neuron-specific genes and serves as a neurogenesis inducer.

EMT inhibitor-1 is a compound that inhibits Hippo and Wnt signaling pathways, as well as TGF- macrophages (TGF-), exhibiting antitumor activity.

NRX-103095 is a potent enhancer of the interaction of β-catenin with the homologous E3 ligase SCFβ-TrCP and enhances the affinity of pSer33 Ser37 β-catenin for β-TrCP with an EC50 of 163 nM.

Pyrvinium pamoate (Pyrvinium embonate) is an old anthelminthic medicine for the treatment of enterobiasis , which re-attracts attention as an anti-cancer drug due to its inhibition of Wnt β-catenin pathway in some types of cancer.

IWP-4 (Inhibitor of Wnt Production-4) is a potent Wnt inhibitor.

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.

JW 67 is an inhibitor of canonical Wnt pathway signaling. JW 67 rapidly reduced active β-catenin with a subsequent downregulation of Wnt target genes, including AXIN2, SP5, and NKD1.

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.

DIF-3 is a chemical compound that acts by activating GSK-3β to facilitate the degradation of cyclin D1 and c-Myc, resulting in reduced expression levels of these proteins. In addition, DIF-3 inhibits Wnt β-catenin signaling pathway-related proteins in DLD-1 cells. This compound exerts a potent antiproliferative effect on the HeLa human cervical cancer cell line by inducing cyclin D1 degradation and inhibiting cyclin D1 mRNA expression [1].

NCB-0846 is an orally active TNIK inhibitor (IC50: 21 nM).

NVP-TNKS656 (TNKS656) is a highly potent, selective, and orally active TNKS2 inhibitor.

CCT251545 is an potent and oral-bioavailable WNT signaling inhibitor(IC50 of 5 nM in 7dF3 cells).

KY19382 (2H-Indol-2-one, 5,6-dichloro-3-[1,3-dihydro-3-(methoxyimino)-2H-indol-2-ylidene]-1,3-dihydro-Ky19382) is a potent and orally active dual inhibitor of CXXC5-DVL and GSK3β( IC50s of 19 and 10 nM, respectively). It activates Wnt β-catenin signaling through inhibitory effects on both CXXC5-DVL interaction and GSK3β activity. KY19382 can be used for the research of high fat diet (HFD) induced metabolic diseases.

Nesuparib (JPI-547 OCN-201) is a potent PARP inhibitor with inhibitory effects on PARP and TNKS1.Nesuparib has antitumor activity and can be used in the treatment of tumors, endocrine and metabolic disorders, genitourinary disorders, and can be used in the study of neuropathic pain, neurodegenerative disorders, and cardiovascular diseases.

Moringin is an isothiocyanate obtained from myrosinase-mediated hydrolysis of the glucosinolate precursor glucoMoringin present in Moringa oleifera seeds. Moringin has anti-inflammatory and antioxidative properties.

BML-284 hydrochloride (Wnt agonist 1 HCL) is a potent, selective Wnt canonical signaling activator and tubulin polymerization inhibitor.

Nefopam hydrochloride (Nefopam HCl) is the hydrochloride salt form of nefopam, a centrally-acting, non-opioid benzoxazocine with analgesic activity.