IPA-3

Names

[ Name ]:
IPA-3

[Synonym ]:
1,1'-Disulfanediyldi(2-naphthol)
1,1'-Dithiodi-2-naphthol
UNII-3XFG6MQ9G2
F0400-0044
2-Naphthalenol, 1,1'-dithiobis-
IPA-3

Biological Activity

[Description]:

IPA-3 is a selective non-ATP competitive PAK1 inhibitor with IC50 of 2.5 μM, and shows no inhibition to group II PAKs (PAKs 4-6).

[Related Catalog]:

Signaling Pathways >> Cell Cycle/DNA Damage >> PAK

Signaling Pathways >> Cytoskeleton >> PAK

Research Areas >> Cancer

[Target]

PAK1:2.5 μM (IC50)

[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[1]. 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[2]. 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[3].

[Kinase Assay]

Pak1 (150 nM final) is pre-incubated with MBP (8.3 μM), indicated proteins, and IPA-3 or DMSO in Kinase buffer for 20 minutes at 4°C. Cdc42-GTPγS (3.2 μM) is then added and the reaction is pre-equilibrated 10 minutes at 30°C. Kinase reactions are started by the addition of ATP (to 30 μM) containing [32P]ATP and are incubated 10 min and analyzed by SDS-PAGE and autoradiography.

[Cell Assay]

Human primary schwannoma cells are grown on 96 well plates for 2 days. Cells are left untreated or treated with 5 µM IPA-3, 20 µM IPA-3 or 20 µM PIR-3.5 for 24 hours. The MTS-solution is left on the cells for 3 hours, before the absorbance at 490 nm is measured. The experiments are conducted three times and mean and standard error of the mean is calculated with Excel.

[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]. Flaiz C, et al. PAK kinase regulates Rac GTPase and is a potential target in human schwannomas. Exp Neurol. 2009 Jul;218(1):137-44.

[3]. 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.

[Related Small Molecules]

PF-3758309 | FRAX 486 | G 5555 | FRAX 597 | FRAX1036 | 5-Aminosalicylic Acid | KPT-9274 | NVS-PAK1-1 | GNE 2861

Chemical & Physical Properties

[ Density]:
1.5±0.1 g/cm3

[ Boiling Point ]:
543.7±35.0 °C at 760 mmHg

[ Melting Point ]:
172℃

[ Molecular Formula ]:
C₂₀H₁₄O₂S₂

[ Molecular Weight ]:
350.454

[ Flash Point ]:
263.4±24.7 °C

[ Exact Mass ]:
350.043518

[ PSA ]:
91.06000

[ LogP ]:
4.96

[ Appearance of Characters ]:
off-white to yellow

[ Vapour Pressure ]:
0.0±1.5 mmHg at 25°C

[ Index of Refraction ]:
1.836

[ Storage condition ]:
Store at +4°C

[ Water Solubility ]:
DMSO: >20mg/mL | Soluble in DMSO or ethanol. Insoluble in water.

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS05, GHS09

[ Signal Word ]:
Danger

[ Hazard Statements ]:
H318-H410

[ Precautionary Statements ]:
P273-P280-P305 + P351 + P338-P501

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi,N

[ Risk Phrases ]:
41-50/53

[ Safety Phrases ]:
26-39-60-61

[ RIDADR ]:
UN 3077 9 / PGIII

[ HS Code ]:
2930909090

Synthetic Route

Click to get detail synthetic route

Precursor & DownStream

Precursor

DownStream

Customs

[ HS Code ]: 2930909090

[ Summary ]:
2930909090. other organo-sulphur compounds. VAT:17.0%. Tax rebate rate:13.0%. . MFN tariff:6.5%. General tariff:30.0%

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