Wnt Inhibitor

IWR-1 (IWR-1-endo) is a tankyrase inhibitor targeting Wnt/β-catenin (IC₅₀ = 180 nM). IWR-1 compromises critical steps of the canonical Wnt signaling, namely translocation of β-catenin to the nucleus and subsequent TCF/LEF activation and expression of Wnt/β-catenin downstream targets. IWR-1 promotes β-catenin phosphorylation by promoting stability of Axin-scaffolded destruction complexes. IWR-1 can be studied in research for anti-tumor purposes, and diseases such as osteosarcoma, colorectal cancer and psoriasis.

Monensin (Monensin A) sodium, an orally active antibiotic, is an ionophore that mediates Na⁺/H⁺ exchange. Monensin sodium is a potent Wnt signaling inhibitor. Monensin sodium causes a marked enlargement of the multivesicular bodies (MVBs) and regulates exosome secretion. Monensin sodium can be used for bacterial, fungal, and parasitic infections research, and shows anticancer effects.

Wnt-C59 (C59) is a highly potent and oral porcupine (PORCN) inhibitor with an IC₅₀ of 74 pM.

MSAB is a potent and selective inhibitor of Wnt/β-catenin signaling. MSAB binds to β-catenin and promotes its degradation, and specifically downregulates Wnt/β-catenin target genes. MSAB exhibits potent anti-tumor effects selectively on Wnt-dependent cancer cells.

FJ9 is a NHERF1/PDZ inhibitor with human NHERF1 PDZ1 IC₅₀ 1540 μM, NHERF1 PDZ2 IC₅₀ 160 μM, and Frizzled-7-Dishevelled PDZ complex K_i 10 μM. FJ9 binds ligand-binding pockets of NHERF1 PDZ domains to block cognate ligand interactions, disrupts Frizzled-7-Dishevelled interactions, and down-regulates canonical Wnt signaling. FJ9 induces apoptosis in cancer cells with intact β-catenin signaling. FJ9 can be used for the research of non-small cell lung cancer, melanoma.

Echinacoside, one of the phenylethanoids isolated from the stems of Cistanche deserticola, effectively inhibits Wnt/β-catenin signaling. Echinacoside elicits neuroprotection by activating Trk receptors and their downstream signal pathways. Antiosteoporotic activity.

Pyrvinium pamoate is an FDA-approved antihelmintic agent that inhibits WNT pathway signaling.

Salinomycin sodium salt (Salinomycin sodium), an antibiotic potassium ionophore, is a potent inhibitor of Wnt/β-catenin signaling. Salinomycin sodium salt acts on the Wnt/Fzd/LRP complex, blocks Wnt-induced LRP6 phosphorylation, and causes degradation of the LRP6 protein. Salinomycin sodium salt shows selective activity against human cancer stem cells.

Adavivint (SM04690; Lorecivivint) is a potent and selective inhibitor of canonical Wnt signaling, with an EC₅₀ of 19.5 nM via a high-throughput TCF/LEF-reporter assay in SW480 colon cancer cells.

PRI-724 is a selective inhibitor of the CBP/β-catenin interaction.

iCRT 14 is a novel potent inhibitor of β-catenin-responsive transcription (CRT), with IC₅₀ of 40.3 nM against Wnt responsive STF16 luciferase.

SKI-II is an oral active and synthetic inhibitor of sphingosine kinase (SK) activity, with IC₅₀ values of 78 μM and 45 μM for SK1 and for SK2, respectively. SKI II causes an irreversible inhibition of SK1 by inducing its lysosomal and/or proteasomal degradation.

Triptonide (NSC 165677) is a natural product identified in Tripterygium wilfordii Hook F.. Triptonide is a Wnt signaling inhibitor with an IC₅₀ of appropriately 0.3 nM. Triptonide has immunosuppression, anti-inflammatory, anti-fertility, neuroprotective and anti-lymphoma effects.

ETC-159 (ETC-1922159) is a potent, orally available PORCN inhibitor. ETC-159 inhibits β-catenin reporter activity with an IC₅₀ of 2.9 nM.

xStAx-VHLL is a β-catenin PROTAC degrader that promotes ubiquitination and proteasome degradation of β-catenin. xStAx-VHLL inhibits the Wnt/β-catenin signaling pathway. xStAx-VHLL can inhibit the proliferation of colon cancer cells and has anti-tumor activity.

Vantictumab (OMP-18R5) is a fully human IgG2 monoclonal antibody. Vantictumab inhibits Wnt pathway signaling by binding to FZD1/2/5/7/8 receptors. Vantictumab can be studied against cancers through direct actions on tumor cells, including CSCs, and effects on the stroma, such as metastatic HER2-negative breast cancer and metastatic pancreatic adenocarcinoma.

IWP-4 is a Wnt inhibitor with an IC₅₀ of 25 nM. IWP-4 specifically inhibits casein kinase 1δ/ε (CK1δ/ε), with an IC₅₀ of 1.06 μM against wild-type CK1δ, 1.02 μM against the CK1δ kinase domain, and 7.07 μM against CK1ε; it shows enhanced inhibitory activity against the M82F CK1δ mutant (IC₅₀ = 0.14 μM). IWP-4 is applicable to research related to cancer, Alzheimer's disease (AD), and heart failure.

Cardamonin can be found from cardamom, and can target various signaling molecules, transcriptional factors, cytokines and enzymes. Cardamonin can inhibit mTOR, NF-κB, Akt, STAT3, Wnt/β-catenin and COX-2. Cardamonin shows anticancer, anti-inflammatory, antimicrobial and antidiabetic activities.

EMT inhibitor-1 is an inhibitor of of Hippo, TGF-β, and Wnt signaling pathways with antitumor activities.

PNU-74654 is an inhibitor of Wnt/β-catenin pathway with an IC₅₀ of 129.8 μM in NCI-H295 cell.