42521-82-4

Basic information

• Product Name: 1,1'-Dithiodi-2-naphthtol
• Synonyms: 1,1'-Dithiodi-2-naphthtol;IPA 3;p21-Activated Kinase Inhibitor III, IPA-3;Bis(2-hydroxy-1-naphthyl) disulfide;2-Naphthalenol, 1,1'-dithiobis-;1,1′-Disulfanediyldinaphthalen-2-ol;1,1'-Disulfanediylbis(naphthalen-2-ol);1-[(2-hydroxy-1-naphthyl)disulfanyl]naphthalen-2-ol
• CAS NO: 42521-82-4
• Molecular Formula: C₂₀H₁₄O₂S₂
• Molecular Weight: 350
• Product Categories: 1,1'-disulfanediylbis(naphthalen-2-ol);PAK Inhibitor III, IPA-3;PAK Inhibitor III;Inhibitors
• Mol File: 42521-82-4.mol
• Article Data: 0

Chemical Properties

• Melting Point: 172℃
• Boiling Point: 543.7±35.0 °C(Predicted)
• Appearance: off-white to yellow/
• Density: 1.46±0.1 g/cm3(Predicted)
• Storage Temp.: Store at +4°C
• Solubility: DMSO: >20mg/mL
• PKA: 7.52±0.50(Predicted)
• Water Solubility: Soluble in DMSO or ethanol. Insoluble in water.
• Sensitive: Light Sensitive
• Stability: Stable for 1 year from date of purchase as supplied. Solutions in DMSO may be stored at -20°C for up to 3 months.
• CAS DataBase Reference: 1,1'-Dithiodi-2-naphthtol(CAS DataBase Reference)
• NIST Chemistry Reference: 1,1'-Dithiodi-2-naphthtol(42521-82-4)
• EPA Substance Registry System: 1,1'-Dithiodi-2-naphthtol(42521-82-4)

Safety Data

• Hazard Codes: Xi,N
• Statements: 41-50/53
• Safety Statements: 26-39-60-61
• RIDADR: UN 3077 9 / PGIII
• WGK Germany: 3
• HazardClass: 9
• Hazardous Substances Data: 42521-82-4(Hazardous Substances Data)

Usage

Description

IPA-3 (42521-82-4) is a selective allosteric inhibitor of Group 1 p21-activated kinase (PAK1 IC50?= 2.5 μM)1?via covalent binding to the PAK1 regulatory domain preventing binding to the upstream activator Cdc422. IPA-3 has been shown to induce cell death in human leukemic cell lines3, significantly inhibit TGFβ1-induced prostate cell epithelial to mesenchymal transition4?and inhibit the growth of liver cancer cells5.

Uses

Different sources of media describe the Uses of 42521-82-4 differently. You can refer to the following data:
1. p21-activated kinase 1 (PAK1) is a member of a family non-receptor serine/threonine kinases that are vital to normal cell function. Binding of various upstream partners to PAK1 results in release of an autoinhibitory domain that blocks activity of the kinase domain. PAK1 expression and activity is upregulated in several human cancers and is a potential therapeutic target for cancer intervention. IPA-3 is a cell-permeable allosteric inhibitor of PAK1 that is non-competitive with respect to ATP binding (IC50 = 2.5 μM). It does not, however, inhibit the activity of PAK1 that has been pre-activated with Cdc42. IPA-3 binds covalently to the PAK1 regulatory domain (apparent Kd = 1.9 uM) and prevents binding to the upstream activator Cdc42.[Cayman Chemical]
2. Acts as an allosteric inhibitor of Pak1

Definition

ChEBI: An organic disulfide obtained by oxidative dimerisation of 1-sulfanylnaphthalen-2-ol.

Biological Activity

IPA-3 is a selective non-ATP competitive Pak1 inhibitor with IC50 of 2.5 μM in a cell-free assay, no inhibition to group II PAKs (PAKs 4-6).

Biochem/physiol Actions

IPA-3 is an allosteric inhibitor of Pak1. It binds to autoinhibitory domain of Pak1 (p21 activated kinase), highly selective amongst kinases. Pak1 is implicated in tumorigenesis and metastasis.

in vitro

IPA-3 is a non ATP-competitive, allosteric inhibitor of p21-activated kinase 1 (Pak1). PIR3.5 is the control compound of IPA-3. IPA-3 prevents Cdc42-stimulated Pak1 autophosphorylation on Thr423. IPA-3 also prevents sphingosine-dependent Pak1 autophosphorylation. IPA-3 does not target exposed cysteine residues on Pak1. The disulfide bond of IPA-3 is critical for inhibition of Pak1 and in vitro reduction by the reducing agent dithiothreitol (DTT) abolishes Pak1 inhibition by IPA-3. IPA-3 inhibits activation of Pak1 by diverse activators, but does not inhibit preactivated Pak1. IPA-3 inhibits PDGF-stimulated Pak activation in mouse embryonic fibroblasts. IPA-3 inhibits Pak1 activation in part by binding covalently to the regulatory domain of Pak1. IPA-3 binds Pak1 covalently in a time- and temperature-dependent manner. IPA-3 prevents binding of the Pak1 activator Cdc42. IPA-3 binds directly to the Pak1 autoregulatory domain. IPA-3 reversibly inhibits PMA-induced membrane ruffling in cells.

References

1) Deacon?et al.?(2008)?An isoform-selective, small-molecule inhibitor targets the autoregulatory mechanism of p21-activated kinase; Chem.Biol.,?14?322 2) Viaud and Peterson (2009)?An allosteric kinase inhibitor binds the p21-activated kinase (PAK) autoregulatory domain covalently; Mol. Cancer Ther.,?8?2559 3) Kuzelova?et al. (2014)?Group 1 PAK Inhibitor IPA-3 Induces Cell Death and Affects Cell Adhesivity to Fibronectin in Human Hematopoietic Cells; PLoS One,?9?e92560 4) Al-Azayzih?et al.?(2015)?P21 Activated Kinase-1 Mediates Transforming Growth factor b1-Induced Prostate Cancer Cell Epithelial to Mesenchymal transition; Biochim. Biophys. Acta,?1853?1229 5) Wong?et al.?(2013)?IPA-3 Inhibits the Growth of Liver Cancer Cells By Suppressing PAK1 and NF-kB Activation; PLoS One,?8?e68843

Upstream product

• 67-66-3 chloroform 
• 135-19-3 β-naphthol 
• 67-56-1 methanol 
• 22791-05-5 naphth<1,2-d>-1,3-oxathiol-2-one 

Downstream Products

• 17096-15-0 1,1'-thiobis(2-naphthol) 
• 858020-92-5 2-acetoxy-1-picrylmercapto-naphthalene 
• 857825-35-5 2-methoxy-1-picrylmercapto-naphthalene 
• 102442-70-6 2-methoxynaphthalen-1-yl disulfide 
• 602-09-5 1,1'-bi-2-naphthol