FRAX486

Catalog No.S7807 Batch:S780701

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Technical Data

Formula

C25H23Cl2FN6O
Molecular Weight 513.39 CAS No. 1232030-35-1
Solubility (25°C)* In vitro DMSO 22 mg/mL (42.85 mM)
Water Insoluble
Ethanol Insoluble
* <1 mg/ml means slightly soluble or insoluble.
* Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations.
* Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.)

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Biological Activity

Description FRAX486 is a potent p21-activated kinase (PAK) inhibitor with IC50 values of 14, 33, 39 and 575 nM for PAK1, PAK2, PAK3 and PAK4 respectively.
Targets
PAK1 [1]
(Cell-free assay)		 PAK2 [1]
(Cell-free assay)		 PAK3 [1]
(Cell-free assay)		 PAK4 [1]
(Cell-free assay)
14 nM 33 nM 39 nM 575 nM
In vitro In WPMY-1 cells, FRAX486 induces concentration-dependent (1-10 μM) degeneration of actin filaments. This was paralleled by attenuation of proliferation rate, being observed from 1 to 10 μM FRAX486. Cytotoxicity of FRAX486 in WPMY-1 cells is time- and concentration-dependent. In WPMY-1 cells, effects of FRAX486 on actin organization, survival, and proliferation occurred already at concentrations of 1-5 μM. In these concentrations, full inhibition of PAK1-3 may be expected, while PAK4 may be inhibited only partially[2].
In vivo FRAX486 crosses the blood-brain barrier and that therapeutically useful concentrations of FRAX486 are in the brain as early as 1 h and remain as long as 24 h after administration, with the maximum concentration in the target tissue at 8 h. Daily dosing results in steady-state levels of FRAX486 in the brain. FRAX486 specifically rescues the Fmr1 KO abnormality in which the spine phenotype is present in apical neurons and not simply decreasing spine density irrespective of genotype or existence of a phenotype. Also, FRAX486 reduces hyperactivity and stereotypical movements, both of which are phenotypes that characterize the mouse model of Fragile X syndrome[3].

Protocol (from reference)

Cell Assay:[2]
  • Cell lines

    WPMY-1 cells(an immortalized cell line obtained from nonmalignant human prostate stroma)

  • Concentrations

    1, 5, 10 μM

  • Incubation Time

    24, 48, 72 h

  • Method

    Cells are grown in 96-well plates (20,000 cells/well) for 24 h, before FRAX486, IPA3, or DMSO are added in indicated concentrations (1, 5, 10 μM). Subsequently, cells are grown for different periods (24, 48, 72 h). Separate controls are performed for each period. At the end of this period, 10 μl of [2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium monosodium salt (WST-8) from CCK-8 is added, and absorbance in each well is measured at 450 nm after incubation for 2 h at 37°C.
Animal Study:[1]
  • Animal Models

    Male C57BL/6 mice

  • Dosages

    3 mg/kg(i.v.) or 30 mg/kg(p.o.)

  • Administration

    i.v. or p.o.

Selleck's FRAX486 has been cited by 10 publications

PAK1 contributes to cerebral ischemia/reperfusion injury by regulating the blood-brain barrier integrity [ iScience, 2023, 26(8):107333] PubMed: 37529106
ERK phosphorylation is dependent on cell adhesion in a subset of pediatric sarcoma cell lines [ Biochim Biophys Acta Mol Cell Res, 2022, 1869(8):119264] PubMed: 35381293
Induction of Wnt signaling antagonists and p21-activated kinase enhances cardiomyocyte proliferation during zebrafish heart regeneration [ J Mol Cell Biol, 2021, 13(1):41-58] PubMed: 33582796
Actionable Cytopathogenic Host Responses of Human Alveolar Type 2 Cells to SARS-CoV-2 [ Mol Cell, 2020, 80(6):1104-1122.e9] PubMed: 33259812
Src-Dependent DBL Family Members Drive Resistance to Vemurafenib in Human Melanoma. [ Cancer Res, 2019, 79(19):5074-5087] PubMed: 31416844
Elucidating essential kinases of endothelin signalling by logic modelling of phosphoproteomics data [ Mol Syst Biol, 2019, 15(8):e8828] PubMed: 31464372
Salmonella stimulates pro-inflammatory signalling through p21-activated kinases bypassing innate immune receptors. [ Nat Microbiol, 2018, 3(10):1122-1130] PubMed: 30224799
PAK4 crystal structures suggest unusual kinase conformational movements. [ Biochim Biophys Acta Proteins Proteom, 2018, 1866(2):356-365] PubMed: 28993291
Protein kinase D1 (PKD1) phosphorylation on Ser203 by type I p21-activated kinase (PAK) regulates PKD1 localization. [ J Biol Chem, 2017, 292(23):9523-9539] PubMed: 28408623
P21-activated kinase 1 regulates resistance to BRAF inhibition in human cancer cells [Babagana M Mol Carcinog, 2017, 56(5):1515-1525] PubMed: 28052407

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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.

NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.