Porcn-IN-2 (Example 107) is a Wnt inhibitor, with an IC50 value of 0.05 nM. Porcn-IN-2 can be used for research of cancer, sarcoma, melanoma, skin cancer, haematological tumors, lymphoma, carcinoma, and leukemia, etc[1].
YB-0158 (Wnt pathway inhibitor 2) is a reverse-turn peptidomimetic and a potent colorectal cancer stem cell (CSC) targeting agent. YB-0158 disrupts Sam68-Src interactions and induces apoptosis in CRC cells. Anti-cancer activities[1].
NSC668036 is a Dishevelled (Dvl) PDZ domain inhibitor with a Kd of 237 µM. NSC668036 blocks Wnt signaling by interrupting the Frizzled-Dvl interaction[1].
ETC-159 is a potent, orally available PORCN inhibitor. It inhibits β-catenin reporter activity with an IC50 of 2.9 nM.
IWP-2-V2 is a IWP-2 (HY-13912) analogue that retains activity against the Wnt/β-catenin pathway[1].
IWR-1 is a tankyrase inhibitor which inhibits Wnt/β-catenin signaling pathway.
N-(3-Methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide is a macamide isolated from Maca (Lepidium meyenii Walp.) N-(3-Methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide induces mesenchymal stem cells osteogenic differentiation and consequent bone formation through activating the canonical Wnt/β‐catenin signaling pathway. N-(3-Methoxybenzyl)-(9Z,12Z,15Z)-octadecatrienamide can be used for the research of osteoporosis[1].
Wnt pathway activator 2 is a potent Wnt activator extracted from patent WO2012024404A1, compound 2, has an IC50s of 13 nM[1].
KY-02327 is an orally active, small molecule inhibitor of the Dishevelled (Dvl)-CXXC5 interaction with IC50 of 3.1 uM, a metabolically stabilized KY-02061 analog; KY-02327 is more stable by 2.3-fold and 1.3-fold than KY-02061 in rat liver microsomes and in human hepatocytes, respectively; shows enhanced effect on induction of ALP activity of osteoblast cells compared with KY-02061; activates the Wnt/β-catenin pathway, promotes osteoblast differentiation, and rescues BMD, bone volume, and trabecular bone structures in variectomized (OVX) mouse model.
Wnt pathway activator 1 is a potent Wnt activator extracted from patent WO2012024404A1, compound 1, has an IC50s of 28-29 nM[1].
PNU-74654 is an inhibitor of Wnt/β-catenin pathway with an IC50 of 129.8 μM in NCI-H295 cell.
SEN461 is a wnt inhibitor.
YW1128 is an inhibitor of Wnt/��-catenin signaling with an IC50 value of 4.1 nM in a reporter assay.
2-Hydroxycinnamaldehyde is a phenylpropanoid that can be isolated from the bark of Cinnamomum cassia. 2-Hydroxycinnamaldehyde inhibits Wnt/β-catenin, STAT3 signaling. 2-Hydroxycinnamaldehyde induces cell apoptosis 2-Hydroxycinnamaldehyde has antitumor and anti-inflammation activities[1][2][3].
Dinactin, an antibiotic ionophore produced by Streptomyces species, as an effective small molecule targeting Wnt/β-catenin signaling pathway in cancer cells. Dinactin shows marked inhibition of HCT-116 cell growth with an IC50 of 1.1 µM. Dinactin shows anti-proliferative activity against the cancer cells in apoptosis-independent manner. Dinactin is also an effective agent for the research of neuropathic pain[1].
KY02111 is a small molecule which can promote differentiation of hPSCs to cardiomyocytes.IC50 value: Target: Wnt signaling inhibitorKY02111 Induces downregulation of Wnt signaling target genes; inhibits canonical Wnt signaling in a manner distinct from other known Wnt inhibitors.KY02111 (10 μM) increases the ratio of beating cardiac colonies as much as 70%-94% in cell aggregates of two hESC lines (KhES-1 and KhES-3), four hiPSC lines (253G1, IMR90-1, IMR90-4, and RCHIPC0003), and a mouse ESC line (R1). KY02111 (10 μM) results in 73%-85% postive IMR90-1 hiPSCs expressing the cardiac markers, cardiac troponin T (cTnT), αActinin, or NKX2.5, whereas only a few DMSO-treated cells are positive for the markers. KY02111 (10 μM) results in 16% postive IMR90-1 hiPSCs expressing the cardiac pacemaker marker, HCN4, whereas the ratio of Vimentin-positive cells (fibroblasts) decreases 3.3-fold. KY02111-induced cardiomyocytes (KY-CMs) expresses the cardiac markers, αMHC, NKH2.5, and HCN4, and that all of the ion channel genes examined are expressed at levels similar to those of adult heart tissue. KY02111 (10 μM) downregulates the expression of 72.7% target genes of canonical WNT signaling in IMR90-1 hiPSCs, suggesting that KY02111 inhibits canonical WNT signaling in hPSCs. KY02111 (10 μM) clearly reduces luciferase activities in both IMR90-1 hiPSCs and HEK293 cells in a dose-dependent manner in the TOPflash assay. KY02111 (10 μM-25 μM) increases cardiac differentiation about 80-fold in transgenic monkey ESCs compared to the control and does not show toxicity to cells even at high concentration. KY02111 (10 μM) significantly reduces luciferase activity in the TOPflash assay in SW480 cells, whereas XAV939 and IWP-2 does not. KY02111 (10 μM) dramatically reduces luciferase activity induced by GSK3β inhibitor BIO in SW480 cells, compared to that of XAV939 and IWP-2. KY02111 alone produces approximately 80% cTnT-positive cells, KY02111 in combination with other WNT inhibitors does not significantly increase differentiation efficiency, which shows that KY02111 effectively produces a high proportion of functional cardiomyocytes from hPSCs [1].
Prodigiosin (Prodigiosine) hydrochloride is a red pigment produced by bacteria as a bioactive secondary metabolite. Prodigiosin hydrochloride is a potent proapoptotic agent, and inhibits Wnt/β-catenin pathway. Prodigiosin hydrochloride has antibacterial, antifungal, antiprotozoal, antimalarial, immunosuppressive, and anticancer properties[1][2].
Berberine chloride hydrate is an alkaloid in several plants with various biological functions, including insulin-sensitizing, anti-inflammatory, and anti-oxidant activity. Berberine chloride hydrate is an AMPK activator.
PDE5-IN-3 (compound 11j) is a potent PDE5 inhibitor with an IC50 of 1.57 nM. PDE5-IN-3 shows moderate EGFR inhibition with IC50 of 5.827 µM. PDE5-IN-3 significantly inhibits the Wnt/β-catenin pathway (IC50=1286.96 ng/mL). PDE5-IN-3 induces the intrinsic apoptotic mitochondrial pathway in HepG2 cells. PDE5-IN-3 has strong antitumor activity[1].
Wnt/β-catenin agonist 1 (compound 3f) is a Wnt/β-catenin signalling pathway agonist, with an EC50 of 0.27 μM[1].
Pyrvinium pamoate is an FDA-approved antihelmintic drug that inhibits WNT pathway signaling.
Salinomycin is an anticoccidial drug with potent anti-bacterial activity and an novel anticancer agent targeting human cancer stem cells.
Hematein is a oxidation product of hematoxylin acted as a dye[1]. Hematein is an allosteric casein kinase II inhibitor with an IC50 of 0.74 μM. Hematein inhibits Akt/PKB Ser129 phosphorylation, the Wnt/TCF pathway and increases apoptosis in lung cancer cells[2].
Gigantol is a bibenzyl compound derived from several medicinal orchids. Giganto shows promising therapeutic potential against cancer cells. Gigantol is a novel inhibitor of the Wnt/β-catenin pathway.
β-catenin inhibitor C2 is a novel potent selective β-catenin inhibitor with Kd of 54.96 nM, directly to ARM domain of β-catenin.β-catenin inhibitor C2 reduced viability of DLD1 and SW480 cells in dose-dependent manner with IC50 ranging between 0.8-1.3 uM, viability of HCT116 and SW48 with IC50 3.45-5.35 uM.β-catenin inhibitor C2 selectively inhibits β-catenin, lowers its cellular load and significantly reduces viability of β-catenin-driven cancer cells.
Adavivint 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.
Neurodazine is an imidazole-based small molecule, serve as a promoter of neurogenesisin pluripotent cells. Neurodazine promotes neurogenesis by activating Wnt and Shh signaling pathways. Neurodazine selectively suppresses astrocyte differentiation of P19 cells[1][2].
CHIR-99021 is a GSK-3α/β inhibitor with an IC50 of 10 and 6.7 nM，showing 500-fold selectivity over its closest homologs CDC2 and ERK2, as well as other protein kinases.
CK2-IN-9 is a potent and selective inhibitor of CK2 kinase with an IC50 of 3 nM. CK2-IN-9 reduces Wnt reporter activity with an IC50 of 75 nM. CK2-IN-9 has low exposure (AUC=0.36 μM/h) and high clearance (CL=65 mL/min/kg) properties in rat[1].
Cardionogen 1 (CDNG1/vuc230) is a Wnt signaling pathway inhibitor that slows down Myc-induced liver tumorigenesis. Cardionogen 1 treatment of zebrafish embryos before gastrulation inhibits cardiomyocyte formation, whereas treatment during or after gastrulation induces cardiomyocyte formation. Cardionogen 1 has potential in research into cancer and cardiovascular disease[1][2].