IPA-3

IPA-3 is a potent and selective PAK1 inhibitor. IPA-3 inhibits the growth of liver cancer cells by suppressing PAK1 and NF-κB activation. IPA-3 treatment significantly inhibited the growth of HCC cells. The mechanisms through which IPA-3 treatment suppresses HCC cell growth are enhancement of apoptosis and blockage of activation of NF-κB. IPA-3 not only inhibits the HCC cell growth, but also suppresses the metastatic potential of HCC cells. Nude mouse xenograft assay demonstrated that IPA-3 treatment significantly reduced the tumor growth rate and decreased tumor volume, indicating that IPA-3 can suppress the in vivo tumor growth of HCC cells. Hepatocellular carcinoma (HCC) is one of the major malignancies worldwide and is associated with poor prognosis due to the high incidences of metastasis and tumor recurrence. Overexpression of p21-activated protein kinase 1 (PAK1) is frequently observed in HCC and is associated with a more aggressive tumor behavior, suggesting that PAK1 is a potential therapeutic target in HCC.

Product information

CAS Number: 42521-82-4

Molecular Weight: 350.45

Formula: C20H14O2S2

Synonym:

IPA 3

IPA3

Chemical Name: 1-[(2-hydroxynaphthalen-1-yl)disulfanyl]naphthalen-2-ol

Smiles: OC1=CC=C2C=CC=CC2=C1SSC1=C2C=CC=CC2=CC=C1O

InChiKey: RFAXLXKIAKIUDT-UHFFFAOYSA-N

InChi: InChI=1S/C20H14O2S2/c21-17-11-9-13-5-1-3-7-15(13)19(17)23-24-20-16-8-4-2-6-14(16)10-12-18(20)22/h1-12,21-22H

Technical Data

Appearance: Solid Power

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

Solubility: DMSO : ≥ 100 mg/mL (285.35 mM)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical or refer to Certificate of Analysis

Storage Condition: Dry, dark and -20 ^oC for 1 year or refer to the Certificate of Analysis.

Shelf Life: ≥12 months if stored properly.

Stock Solution Storage: 0 - 4 ^oC for 1 month or refer to the Certificate of Analysis.

Drug Formulation: To be determined

HS Tariff Code: 382200

How to use

In Vitro:

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. IPA-3 (2 µM, 5 µM or 20 µM) reduces cell spreading in human primary Schwann and schwannoma cells. IPA-3 treatment significantly reduces the number of adherent Schwann and schwannoma cells in a dose-dependent manner. 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.

References:

1. Viaud J, et al. An allosteric kinase inhibitor binds the p21-activated kinase autoregulatory domain covalently. Mol Cancer Ther. 2009 Sep;8(9):2559-65.
2. Deacon SW, et al. An isoform-selective, small-molecule inhibitor targets the autoregulatory mechanism of p21-activated kinase. Chem Biol. 2008 Apr;15(4):322-31

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