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IPA-3

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Chemical Structure| 42521-82-4 同义名 : -
CAS号 : 42521-82-4
货号 : A427173
分子式 : C20H14O2S2
纯度 : 99%+
分子量 : 350.454
MDL号 : MFCD00388917
存储条件：

粉末 Sealed in dry,2-8°C

液体 -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 40 mg/mL(114.14 mM)，配合低频超声，并水浴加热至45℃助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
靶点

  • PAK

    PAK1, IC50:2.5 μM

  • PAK1

    PAK1, IC50:2.5 μM
描述 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[3]. 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[4]. 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[5]. Targeting PAK1 using IPA-3, significantly inhibits the murine metastatic PCa (RM1) cell proliferation and motility in vitro, and metastasis to the lungs in vivo[6]. Compared with spinal cord injury SCI + vehicle mice, IPA-3 treatment showed decreased p-PAK1, MMP-2, MMP-9, cleaved caspase-3, TNF-α, and IL-1β expression. Moreover, inhibition of PAK1 by IPA-3 reduced spinal cord water content and Evans blue extravasation, increased neuronal survival, and reduced TUNEL-positive cells at 24 hours after SCI[7].
细胞研究
细胞系 浓度 检测类型 检测时间 活动说明 数据源
human 786-0 cell Growth inhibition assay Inhibition of human 786-0 cell growth in a cell viability assay, IC50=3.31805 μM SANGER
human 8305C cell Growth inhibition assay Inhibition of human 8305C cell growth in a cell viability assay, IC50=4.16758 μM SANGER
human A2780 cell Growth inhibition assay Inhibition of human A2780 cell growth in a cell viability assay, IC50=28.371 μM SANGER
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

2.85mL

0.57mL

0.29mL

14.27mL

2.85mL

1.43mL

28.53mL

5.71mL

2.85mL
参考文献

[1]Viaud J, Peterson JR. An allosteric kinase inhibitor binds the p21-activated kinase autoregulatory domain covalently. Mol Cancer Ther. 2009 Sep;8(9):2559-65.

[2]Deacon SW, Beeser A, et al. An isoform-selective, small-molecule inhibitor targets the autoregulatory mechanism of p21-activated kinase. Chem Biol. 2008 Apr;15(4):322-31.

[3]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.

[4]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.

[5]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

[6]Arti Verma,et al. PAK1 inhibitor IPA-3 mitigates metastatic prostate cancer-induced bone remodeling. Biochem Pharmacol. 2020 Jul;177:113943.

[7]Xinran Ji,et al. Inhibition of p21-Activated Kinase 1 by IPA-3 Promotes Locomotor Recovery After Spinal Cord Injury in Mice. Spine (Phila Pa 1976). 2016 Jun;41(11):919-925.