PNU 74654

Names

[ Name ]:
PNU 74654

[Synonym ]:
Benzoic acid, 2-phenoxy-, 2-[(1E)-(5-methyl-2-furanyl)methylene]hydrazide
N'-[(E)-(5-Methyl-2-furyl)methylene]-2-phenoxybenzohydrazide
N'-[(E)-(5-methylfuran-2-yl)methylidene]-2-phenoxybenzohydrazide
PNU-74654

Biological Activity

[Description]:

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

[Related Catalog]:

Signaling Pathways >> Stem Cell/Wnt >> β-catenin

Signaling Pathways >> Stem Cell/Wnt >> Wnt

Research Areas >> Cancer

[Target]

129.8 μM (Wnt/β-catenin, NCI-H295 cell)[1]

[In Vitro]

PNU-74654 binds to β-catenin with a KD of 450 nM. The Tcf3/Tcf4-binding surface on β-catenin contains a well-defined hot spot around residues K435 and R469. The binding mode of PNU-74654 involves the two narrow pockets on either side of this hot spot[2]. In NCI-H295 cells,PNU-74654 significantly decreases cell proliferation 96 h after treatment, increases early and late apoptosis, decreases nuclear beta-catenin accumulation, impairs CTNNB1/beta-catenin expression and increases beta-catenin target genes 48 h after treatment. No effects are observed on HeLa cells. In NCI-H295 cells, PNU-74654 decreases cortisol, testosterone and androstenedione secretion 24 and 48 h after treatment. The SF1 and CYP21A2 mRNA expression as well as the protein levels of STAR and aldosterone synthase are decreased in NCI-H295 cells after 48 h PNU-74654 treatment. In Y1 cells, PNU-74654 impairs corticosterone secretion 24 h after treatment but does not decrease cell viability[1].

[Cell Assay]

The PNU-74654 compound is dissolved in DMSO at stock concentrations of 31.2 mM. For working solutions, PNU-74654 is diluted 100X in growth medium with no serum deprivation. NCI-H295 cells are plated at 200,000 cells per well in 24-well plates for gene expression, protein analysis and adrenal steroid measurements. After 48 h, cells are treated with vehicle (0.1%-0.4% DMSO) or 10, 50, 100 and 200 μM PNU-74654. After 24 and 48 h, medium supernatants are collected for adrenal steroid measurements[1].

[References]

[1]. Leal LF, et al. Inhibition of the Tcf/beta-catenin complex increases apoptosis and impairs adrenocortical tumor cell proliferation and adrenal steroidogenesis. Oncotarget. 2015 Dec 15;6(40):43016-32.

[2]. Trosset JY, et al. Inhibition of protein-protein interactions: the discovery of druglike beta-catenin inhibitors by combining virtual and biophysical screening. Proteins. 2006 Jul 1;64(1):60-7.

[Related Small Molecules]

XAV-939 | ICG-001 | Salinomycin | IWR-1 | Wnt-C59 | Berberine chloride hydrate | Pyrvinium pamoate | ETC-159 | BML 284 | IWP-2 | Heparan Sulfate | KYA 1797K | FH535 | SKL2001 | CCT251545

Chemical & Physical Properties

[ Density]:
1.2±0.1 g/cm3

[ Molecular Formula ]:
C₁₉H₁₆N₂O₃

[ Molecular Weight ]:
320.342

[ Exact Mass ]:
320.116089

[ PSA ]:
63.83000

[ LogP ]:
3.90

[ Index of Refraction ]:
1.593

[ Storage condition ]:
-20℃

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ RIDADR ]:
NONH for all modes of transport

Articles

An increase in glucosylceramide synthase induces Bcl-xL-mediated cell survival in vinorelbine-resistant lung adenocarcinoma cells.

Oncotarget 6 , 20513-24, (2015)

Reversing drug resistance with concurrent treatment confers anticancer benefits. In this study, we investigated the potential mechanism of glucosylceramide synthase (GCS)-mediated vinca alkaloid vinor...

The WTX Tumor Suppressor Interacts with the Transcriptional Corepressor TRIM28.

J. Biol. Chem. 290 , 14381-90, (2015)

WTX encodes a tumor suppressor implicated in the pediatric kidney cancer Wilms tumor and in mesenchymal differentiation with potentially distinct functions in the cytoplasm, at the plasma membrane, an...

Inhibition of the Tcf/beta-catenin complex increases apoptosis and impairs adrenocortical tumor cell proliferation and adrenal steroidogenesis.

.PubMed ID

To date, there is no effective therapy for patients with advanced/metastatic adrenocortical cancer (ACC). The activation of the Wnt/beta-catenin signaling is frequent in ACC and this pathway is a prom...

Related Compounds

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