PNU-74654

Cas：113906-27-7

Product Information：

PNU-74654 is a novel inhibitor of the interaction between ß-catenin and T cell factor 4 (Tcf4), disrupting the Wnt signaling pathway.

Chemical Formula: C19H16N2O3

Exact Mass: 320.1161

Molecular Weight: 320.348

Elemental Analysis: C, 71.24; H, 5.03; N, 8.74; O, 14.98

Chemical Name:

2-Phenoxybenzoic acid-[(5-methyl-2-furanyl)methylene]hydrazide

InChi Key: 

JJEDWBQZCRESJL-DEDYPNTBSA-N

InChi Code: 

InChI=1S/C19H16N2O3/c1-14-11-12-16(23-14)13-20-21-19(22)17-9-5-6-10-18(17)24-15-7-3-2-4-8-15/h2-13H,1H3,(H,21,22)/b20-13+

Smiles Code:

O=C(N/N=C/C1=CC=C(C)O1)C2=CC=CC=C2OC3=CC=CC=C3

Technical Data：

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO

Shelf Life: >2 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

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.

References:

1. Taiyab A, Korol A, Deschamps PA, West-Mays JA. β-Catenin/CBP-Dependent Signaling Regulates TGF-β-Induced Epithelial to Mesenchymal Transition of Lens Epithelial Cells. Invest Ophthalmol Vis Sci. 2016 Oct 1;57(13):5736-5747. doi: 10.1167/iovs.16-20162. PubMed PMID: 27787561; PubMed Central PMCID: PMC5089212.

2. Wang H, Graves MW 2nd, Zhou H, Gu Z, Lamont RJ, Scott DA. 2-Amino-4-(3,4-(methylenedioxy)benzylamino)-6-(3-methoxyphenyl)pyrimidine is an anti-inflammatory TLR-2, -4 and -5 response mediator in human monocytes. Inflamm Res. 2016 Jan;65(1):61-9. doi: 10.1007/s00011-015-0891-0. Epub 2015 Nov 27. PubMed PMID: 26613980; PubMed Central PMCID: PMC4703520.

3. Leal LF, Bueno AC, Gomes DC, Abduch R, de Castro M, Antonini SR. 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. doi: 10.18632/oncotarget.5513. PubMed PMID: 26515592; PubMed Central PMCID: PMC4767488.

4. Pradhan A, Olsson PE. Juvenile ovary to testis transition in zebrafish involves inhibition of ptges. Biol Reprod. 2014 Aug;91(2):33. doi: 10.1095/biolreprod.114.119016. Epub 2014 Jun 11. PubMed PMID: 24920039.

Products are for research use only. Not for human use.