VPC-14337

Cas：3546-41-6

Product Information：

VPC-14337 is an nhibitor of the transcriptional activity of full-length/splice variant Ars.

Chemical Formula: C75H70N6O6

Exact Mass: 1150.5357

Molecular Weight: 1151.42

Elemental Analysis: C, 78.24; H, 6.13; N, 7.30; O, 8.34

Synonym:

Pyrvinium pamoate

Pyrvinium embonate

Viprynium embonate

Chemical Name:

(E)-2-(2-(2,5-dimethyl-1-phenyl-1H-pyrrol-3-yl)vinyl)-6-(dimethylamino)-1-methylquinolin-1-ium 4,4'-methylenebis(3-hydroxy-2-naphthoate)

InChi Key:

OOPDAHSJBRZRPH-UHFFFAOYSA-L

InChi Code: 

InChI=1S/2C26H28N3.C23H16O6/c2*1-19-17-21(20(2)29(19)24-9-7-6-8-10-24)11-13-23-14-12-22-18-25(27(3)4)15-16-26(22)28(23)5;24-20-16(14-7-3-1-5-12(14)9-18(20)22(26)27)11-17-15-8-4-2-6-13(15)10-19(21(17)25)23(28)29/h2*6-18H,1-5H3;1-10,24-25H,11H2,(H,26,27)(H,28,29)/q2*+1;/p-2

Smiles Code:

CN(C)C1=CC2=C([N+](C)=C(/C=C/C3=C(C)N(C4=CC=CC=C4)C(C)=C3)C=C2)C=C1.CN(C)C5=CC6=C([N+](C)=C(/C=C/C7=C(C)N(C8=CC=CC=C8)C(C)=C7)C=C6)C=C5.[O-]C(C9=CC%10=C(C=CC=C%10)C(CC%11=C(O)C(C([O-])=O)=CC%12=C%11C=CC=C%12)=C9O)=O

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：

Pyrvinium pamoate (0-500 nM) inhibits proliferation of MCF-7 (luminal), MDA-MB-231 (claudin-low), MDA-MB-468 (basal-like) and SkBr3 (HER2-OE) cells in a dose-dependent manner, with IC50 value of 1170±105.0 nM against MDA-MB-231 cell line. Pyrvinium pamoate significantly inhibits self-renewal and proliferation of BCSCs, and suppresses BCSC population with a distinct phenotype. Pyrvinium pamoate significantly decreases average expression levels of FZD1, FZD10, WNT1, WNT7B, CTNNB1, MYC, and LRP5 at transcriptional level. Moreover, Pyrvinium pamoate also efficiently down-regulates the expression of other stemness genes including ALDH1, CD44 and ABCG2. Pyrvinium pamoate blocks colon cancer cell growth in vitro in a dose-dependent manner with great differences in the inhibitory concentration (IC50), ranging from 0.6 to 65 μM for colon cancer cells with mutations in WNT signaling. Pyrvinium pamoate decreases messenger RNA (mRNA) and protein levels of known WNT target genes as c-MYC and thereby led to the induction of p21. Pyrvinium pamoate ultimately inhibits Wnt signalling despite its lack of efficacy on CK1. Pyrvinium pamoate imposes specific toxicity on cardiac fibroblasts in ischemia (IC50=9.5 nM). The cytotoxic effect of Pyrvinium pamoate on cardiac fibroblasts specifically under glucose- and glutamine-deficient condition.

In Vivo：

In the xenograft model, Pyrvinium pamoate (500 nM)-pretreatment strongly delays tumor size and tumor weight, and the tumor volume is markedly decreased.

References：

1. Xu L, et al. WNT pathway inhibitor pyrvinium pamoate inhibits the self-renewal and metastasis of breast cancer stem cells. Int J Oncol. 2016 Mar;48(3):1175-86.

2. Wiegering A, et al. The impact of pyrvinium pamoate on colon cancer cell viability. Int J Colorectal Dis. 2014 Oct;29(10):1189-98.

3. Venerando A, et al. Pyrvinium pamoate does not activate protein kinase CK1, but promotes Akt/PKB down-regulation and GSK3 activation. Biochem J. 2013 May 15;452(1):131-7.

4. Murakoshi M, et al. An anthelmintic drug, pyrvinium pamoate, thwarts fibrosis and ameliorates myocardial contractile dysfunction in a mouse model of myocardial infarction. PLoS One. 2013 Nov 4;8(11):e79374.

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