PNU-74654 | CAS#113906-27-7

MedKoo Cat#: 525354 | Name: PNU-74654

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Description:

WARNING: This product is for research use only, not for human or veterinary use.

PNU-74654 is a novel inhibitor of the interaction between ß-catenin and T cell factor 4 (Tcf4), disrupting the Wnt signaling pathway. PNU-74654 suppresses cytoplasmic and nuclear beta-catenin and impaired the NF-kappaB pathway.

Chemical Structure

PNU-74654

CAS#113906-27-7

Theoretical Analysis

MedKoo Cat#: 525354

Name: PNU-74654

CAS#: 113906-27-7

Chemical Formula: C19H16N2O3

Exact Mass: 320.1161

Molecular Weight: 320.35

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

Price and Availability

Size	Price	Availability
1mg	USD 350.00	2 Weeks
5mg	USD 600.00	2 Weeks
10mg	USD 750.00	2 Weeks

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Related CAS #

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Synonym

PNU-74654

IUPAC/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

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

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

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

In vitro activity:

In NCI-H295 cells, PNU-74654 significantly decreased cell proliferation 96 h after treatment, increased early and late apoptosis, decreased nuclear beta-catenin accumulation, impaired CTNNB1/beta-catenin expression and increased beta-catenin target genes 48 h after treatment. No effects were observed on HeLa cells. In NCI-H295 cells, PNU-74654 decreased cortisol, testosterone and androstenedione secretion 24 and 48 h after treatment. Additionally, in NCI-H295 cells, PNU-74654 decreased SF1 and CYP21A2 mRNA expression as well as the protein levels of STAR and aldosterone synthase 48 h after treatment. In Y1 cells, PNU-74654 impaired corticosterone secretion 24 h after treatment but did not decrease cell viability. Reference: Oncotarget. 2015 Dec 15;6(40):43016-32. https://pubmed.ncbi.nlm.nih.gov/26515592/

In vivo activity:

This study used a xenograft model of CRC to investigate PNU-74654 activity alone and in combination with 5-FU follow by histological staining and biochemical and gene expression analyses by RT-PCR and western blot. PNU-74654 inhibited cell-growth and synergistically affected the anti-tumor properties of 5-FU via modulation of Cyclin D1 and survivin. This agent inhibited the migration/invasion of colorectal cancer cells via perturbation of E-cadherin. Furthermore, PNU-74654 inhibited the tumor growth, which was more pronounced using the PNU-74654 plus 5-FU combination via induction of reactive oxygen species, down-regulation of SOD and modulation of MCP-1, P53, TNF-α. Reference: Tissue Cell. 2022 Aug;77:101853. https://pubmed.ncbi.nlm.nih.gov/35803035/

	Solvent	mg/mL	mM
Solubility
	DMF	30.0	93.65
	DMF:PBS (pH 7.2) (1:1)	0.5	1.56
	DMSO	29.0	90.56
	Ethanol	1.0	3.12

Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.

Preparing Stock Solutions

The following data is based on the product molecular weight 320.35 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Wu MY, Wang CC, Chang YC, Yu CY, Sung WW, Chen CJ, Tsai MC. The Therapeutic Role of PNU-74654 in Hepatocellular Carcinoma May Involve Suppression of NF-κB Signaling. Medicina (Kaunas). 2022 Jun 14;58(6):798. doi: 10.3390/medicina58060798. PMID: 35744061; PMCID: PMC9228701. 2. 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. PMID: 26515592; PMCID: PMC4767488. 3. Amerizadeh F, Rahmani F, Maftooh M, Nasiri SN, Hassanian SM, Giovannetti E, Moradi-Marjaneh R, Sabbaghzadeh R, Shahidsales S, Joudi-Mashhad M, Ghayour-Mobarhan M, Ferns GA, Khazaei M, Avan A. Inhibition of the Wnt/b-catenin pathway using PNU-74654 reduces tumor growth in in vitro and in vivo models of colorectal cancer. Tissue Cell. 2022 Aug;77:101853. doi: 10.1016/j.tice.2022.101853. Epub 2022 Jun 15. PMID: 35803035.

In vitro protocol:

In vivo protocol:

1. Amerizadeh F, Rahmani F, Maftooh M, Nasiri SN, Hassanian SM, Giovannetti E, Moradi-Marjaneh R, Sabbaghzadeh R, Shahidsales S, Joudi-Mashhad M, Ghayour-Mobarhan M, Ferns GA, Khazaei M, Avan A. Inhibition of the Wnt/b-catenin pathway using PNU-74654 reduces tumor growth in in vitro and in vivo models of colorectal cancer. Tissue Cell. 2022 Aug;77:101853. doi: 10.1016/j.tice.2022.101853. Epub 2022 Jun 15. PMID: 35803035.

1: Chien TL, Wu YC, Lee HL, Sung WW, Yu CY, Chang YC, Lin CC, Wang CC, Tsai MC. PNU-74654 Induces Cell Cycle Arrest and Inhibits EMT Progression in Pancreatic Cancer. Medicina (Kaunas). 2023 Aug 24;59(9):1531. doi: 10.3390/medicina59091531. PMID: 37763649; PMCID: PMC10532988. 2: Liu C, Zhou D, Zhang Q, Wei H, Lu Y, Li B, Zhan H, Cheng J, Wang C, Yang Y, Li S, Hu C, Liao X. Transcription factor EB (TFEB) improves ventricular remodeling after myocardial infarction by inhibiting Wnt/β-catenin signaling pathway. PeerJ. 2023 Aug 18;11:e15841. doi: 10.7717/peerj.15841. PMID: 37609444; PMCID: PMC10441526. 3: Bai S, Shao J, Bi C, Li F. β-asarone attenuates the proliferation, migration and enhances apoptosis of retinoblastoma through Wnt/β-catenin signaling pathway. Int Ophthalmol. 2023 May;43(5):1687-1699. doi: 10.1007/s10792-022-02566-1. Epub 2022 Nov 13. PMID: 36372820. 4: Yan W, Zheng L, Xu X, Hao Z, Zhang Y, Lu J, Sun Z, Dai J, Shi D, Guo B, Jiang Q. Heterozygous LRP1 deficiency causes developmental dysplasia of the hip by impairing triradiate chondrocytes differentiation due to inhibition of autophagy. Proc Natl Acad Sci U S A. 2022 Sep 13;119(37):e2203557119. doi: 10.1073/pnas.2203557119. Epub 2022 Sep 6. PMID: 36067312; PMCID: PMC9477389. 5: Albalawi YA, Narasipura SD, Al-Harthi L. Wnt/β-Catenin Protects Lymphocytes from HIV-Mediated Apoptosis via Induction of Bcl-xL. Viruses. 2022 Jul 2;14(7):1469. doi: 10.3390/v14071469. PMID: 35891449; PMCID: PMC9324643. 6: Amerizadeh F, Rahmani F, Maftooh M, Nasiri SN, Hassanian SM, Giovannetti E, Moradi-Marjaneh R, Sabbaghzadeh R, Shahidsales S, Joudi-Mashhad M, Ghayour- Mobarhan M, Ferns GA, Khazaei M, Avan A. Inhibition of the Wnt/b-catenin pathway using PNU-74654 reduces tumor growth in in vitro and in vivo models of colorectal cancer. Tissue Cell. 2022 Aug;77:101853. doi: 10.1016/j.tice.2022.101853. Epub 2022 Jun 15. PMID: 35803035. 7: Wu MY, Wang CC, Chang YC, Yu CY, Sung WW, Chen CJ, Tsai MC. The Therapeutic Role of PNU-74654 in Hepatocellular Carcinoma May Involve Suppression of NF-κB Signaling. Medicina (Kaunas). 2022 Jun 14;58(6):798. doi: 10.3390/medicina58060798. PMID: 35744061; PMCID: PMC9228701. 8: Chen WJ, Sung WW, Yu CY, Luan YZ, Chang YC, Chen SL, Lee TH. PNU-74654 Suppresses TNFR1/IKB Alpha/p65 Signaling and Induces Cell Death in Testicular Cancer. Curr Issues Mol Biol. 2022 Jan 4;44(1):222-232. doi: 10.3390/cimb44010016. PMID: 35723395; PMCID: PMC8928937. 9: Qi X, Sun Z, Li X, Jiao Y, Chen S, Song P, Qian Z, Qian J, Qiu X, Tang L. Shp2 suppresses fat accumulation in white adipose tissue by activating Wnt/β-catenin signaling following vertical sleeve gastrectomy in obese rats with type-2 diabetes. Exp Ther Med. 2022 Apr;23(4):302. doi: 10.3892/etm.2022.11231. Epub 2022 Feb 22. PMID: 35340882; PMCID: PMC8931631. 10: Jiang Y, Li S, Zhou Q, Liu S, Liu X, Xiao J, Jiang W, Xu Y, Kong D, Wang F, Wei F, Zheng C. PDCD4 Negatively Regulated Osteogenic Differentiation and Bone Defect Repair of Mesenchymal Stem Cells Through GSK-3β/β-Catenin Pathway. Stem Cells Dev. 2021 Aug 15;30(16):806-815. doi: 10.1089/scd.2021.0041. Epub 2021 Jul 2. PMID: 34088227. 11: Maria AG, Silva Borges K, Lira RCP, Hassib Thomé C, Berthon A, Drougat L, Kiseljak-Vassiliades K, Wierman ME, Faucz FR, Faça VM, Tone LG, Stratakis CA. Inhibition of Aurora kinase A activity enhances the antitumor response of beta- catenin blockade in human adrenocortical cancer cells. Mol Cell Endocrinol. 2021 May 15;528:111243. doi: 10.1016/j.mce.2021.111243. Epub 2021 Mar 11. PMID: 33716050; PMCID: PMC8297658. 12: Takam Kamga P, Dal Collo G, Cassaro A, Bazzoni R, Delfino P, Adamo A, Bonato A, Carbone C, Tanasi I, Bonifacio M, Krampera M. Small Molecule Inhibitors of Microenvironmental Wnt/β-Catenin Signaling Enhance the Chemosensitivity of Acute Myeloid Leukemia. Cancers (Basel). 2020 Sep 21;12(9):2696. doi: 10.3390/cancers12092696. PMID: 32967262; PMCID: PMC7565567. 13: Yang T, Sun W, Duan YH, Sun YB, Ren YM, Hou WY, Tian MQ. Vitamin D3 protects articular cartilage by inhibiting the Wnt/β-catenin signaling pathway. Exp Ther Med. 2020 Aug;20(2):1775-1781. doi: 10.3892/etm.2020.8839. Epub 2020 Jun 4. PMID: 32742408; PMCID: PMC7388321. 14: Ma X, Xiang F, Pei Z, Miao J, Wu P, Song X, Li Y, Zhang Y. Circ-Smad5 retards the G1/S transition of cell cycle via inhibiting the activity of wnt/lef/cyclind1 signaling in JB6 cells. Genes Dis. 2020 Jan 9;8(3):364-372. doi: 10.1016/j.gendis.2020.01.001. PMID: 33997183; PMCID: PMC8093577. 15: Wu L, Zhou Z, Han S, Chen J, Liu Z, Zhang X, Yuan W, Ji J, Shu X. PLAGL2 promotes epithelial-mesenchymal transition and mediates colorectal cancer metastasis via β-catenin-dependent regulation of ZEB1. Br J Cancer. 2020 Feb;122(4):578-589. doi: 10.1038/s41416-019-0679-z. Epub 2019 Dec 12. PMID: 31827238; PMCID: PMC7028997. 16: Liu WG, Xu Q. Upregulation of circHIPK3 promotes the progression of gastric cancer via Wnt/β-catenin pathway and indicates a poor prognosis. Eur Rev Med Pharmacol Sci. 2019 Sep;23(18):7905-7912. doi: 10.26355/eurrev_201909_19004. PMID: 31599413. 17: Fasihi A, Soltani BM, Ranjbaran ZS, Bahonar S, Norouzi R, Nasiri S. Hsa- miR-942 fingerprint in colorectal cancer through Wnt signaling pathway. Gene. 2019 Sep 5;712:143958. doi: 10.1016/j.gene.2019.143958. Epub 2019 Jul 3. PMID: 31278963. 18: Rahmani F, Amerizadeh F, Hassanian SM, Hashemzehi M, Nasiri SN, Fiuji H, Ferns GA, Khazaei M, Avan A. PNU-74654 enhances the antiproliferative effects of 5-FU in breast cancer and antagonizes thrombin-induced cell growth via the Wnt pathway. J Cell Physiol. 2019 Aug;234(8):14123-14132. doi: 10.1002/jcp.28104. Epub 2019 Jan 11. PMID: 30633353. 19: Wu L, Xie J, Jiang L, Su T, Ye L, Zhou W, Jiang Y, Zhang C, Ning G, Wang W. Feminizing Adrenocortical Carcinoma: The Source of Estrogen Production and the Role of Adrenal-Gonadal Dedifferentiation. J Clin Endocrinol Metab. 2018 Oct 1;103(10):3706-3713. doi: 10.1210/jc.2018-00689. PMID: 30053001. 20: Fasihi A, M Soltani B, Atashi A, Nasiri S. Introduction of hsa-miR-103a and hsa-miR-1827 and hsa-miR-137 as new regulators of Wnt signaling pathway and their relation to colorectal carcinoma. J Cell Biochem. 2018 Jul;119(7):5104-5117. doi: 10.1002/jcb.26357. Epub 2018 Mar 7. PMID: 28817181.