IPA-3

Bezeichnung:IPA-3

CAS-Nr42521-82-4

Englisch Name:IPA-3

CBNumberCB02518903

SummenformelC20H14O2S2

Molgewicht350.45

MOL-Datei42521-82-4.mol

IPA-3 physikalisch-chemischer Eigenschaften

Schmelzpunkt	172℃
Siedepunkt	543.7±35.0 °C(Predicted)
Dichte	1.46±0.1 g/cm3(Predicted)
storage temp.	2-8°C
Löslichkeit	DMSO: >20mg/mL
pka	7.52±0.50(Predicted)
Aggregatzustand	Yellow solid
Farbe	off-white to yellow
Wasserlöslichkeit	Soluble in DMSO or ethanol. Insoluble in water.
Sensitive	Light Sensitive
Stabilität	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 Datenbank	42521-82-4

Sicherheit

Kennzeichnung gefährlicher	Xi,N
R-Sätze:	41-50/53
S-Sätze:	26-39-60-61
RIDADR	UN 3077 9 / PGIII
WGK Germany	3
HazardClass	9

Gefahreninformationscode (GHS)

IPA-3 Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
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.
Verwenden
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]
Verwenden
Acts as an allosteric inhibitor of Pak1
Definition
ChEBI: An organic disulfide obtained by oxidative dimerisation of 1-sulfanylnaphthalen-2-ol.
Biologische Aktivität
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.
Lager
Store at -20°C
Einzelnachweise
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

IPA-3 Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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