FRAX486
Based on 10 publication(s) in Google Scholar
FRAX486 is a p21-activated kinase (PAK) inhibitor with IC50s of 14, 33 and 39 nM for PAK1, PAK2 and PAK3, respectively.
For research use only. We do not sell to patients.
- Purity: 98.10%
- CAS No.: 1232030-35-1
- Formula: C25H23Cl2FN6O
- Molecular Weight:513.39
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Storage:Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 2 years , -20°C, 1 year
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Protocol
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) FRAX486
More- Mol Cell. 2021 Oct 7;81(19):4076-4090.e8. [Abstract]
- Am J Hum Genet. 2018 Oct 4;103(4):579-591. [Abstract]
- Br J Cancer. 2023 Jan;128(1):148-159. [Abstract]
- Cell Biosci. 2023 Jan 20;13(1):13. [Abstract]
- J Chem Inf Model. 2024 Jun 24;64(12):4835-4849. [Abstract]
- Int J Mol Sci. 2024 Sep 21;25(18):10138. [Abstract]
- Braz J Med Biol Res. 2024 Jul 1:57:e13357. [Abstract]
- bioRxiv. 2024 Oct 22:2024.10.22.619411. [Abstract]
- University of Zürich. 2021 Dec.
- bioRxiv. 2020 Jun.
Biological Activity
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PAK1 14 nM (IC50) |
PAK2 33 nM (IC50) |
PAK3 39 nM (IC50) |
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Cell Line
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Type | Value | Description | References |
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| Cortical neurone | EC50 |
500 nM
Compound: FRAX486
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Effect on DISC1 knockdown-elicited synaptic changes in rat cortical neurons assessed as prevention of spine size reduction preincubated for 60 mins followed by APV WD solution addition and measured after 20 mins by immunofluorescence analysis
Effect on DISC1 knockdown-elicited synaptic changes in rat cortical neurons assessed as prevention of spine size reduction preincubated for 60 mins followed by APV WD solution addition and measured after 20 mins by immunofluorescence analysis
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[PMID: 27071060] |
In vitro kinase assays using pure enzymes reveal IC50s for FRAX486 between 10-100 nM for PAK1-3, while the IC50 of 779 nM for PAK4 is just below the micromolar range. For FRAX486, an EC50 value of 500 nM has been reported from cells (5-50 fold higher than IC50). FRAX486 (30 μM) inhibits endothelin-1 and -2 induced contractions. In WPMY-1 cells, FRAX486 (24 h) induces concentration-dependent (1-10 μM) degeneration of actin filaments. This is 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. FRAX486 significantly reduces the relative proliferation rate in the remaining populations of WPMY-1 cells. While 68% of solvent-treated (24 h) cells shows proliferation, proliferation rate after application of FRAX486 (1-10 μM, 24 h) ranges around 45%. FRAX486 (1-10 μM, 24 h) causes concentration-dependent degeneration of actin filaments. Actin filaments in solvent-treated control cells are arranged to bundles, forming long and thin protrusions, with elongations from adjacent cells overlapping each other. FRAX486 in concentrations of 1 μM causes partial loss of actin organization, including regressing degree of actin polymerization and degeneration of protrusions. FRAX486 in concentrations of 5 or 10 μM causes complete breakdown of filament organization, resulting in a rounded cell shape without protrusions[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Chemical Information
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CAS No. 1232030-35-1
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Appearance Solid
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Molecular Weight 513.39
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Formula C25H23Cl2FN6O
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Color Light yellow to yellow
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SMILES
FC1=CC(NC2=NC=C3C(N(CC)C(C(C4=CC=C(Cl)C=C4Cl)=C3)=O)=N2)=CC=C1N5CCNCC5
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Powder -20°C 3 years 4°C 2 years In solvent -80°C 2 years -20°C 1 year
Publications (10)
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Journal Impact Factor
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Most Recent
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Mol Cell
A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies. [Abstract]2021 Oct 7;81(19):4076-4090.e8. PMID: 34375582 -
Am J Hum Genet
Activating Mutations in PAK1, Encoding p21-Activated Kinase 1, Cause a Neurodevelopmental Disorder. [Abstract]2018 Oct 4;103(4):579-591. PMID: 30290153 -
Br J Cancer
2023 Jan;128(1):148-159. PMID: 36319849 -
Cell Biosci
Hypofucosylation of Unc5b regulated by Fut8 enhances macrophage emigration and prevents atherosclerosis. [Abstract]2023 Jan 20;13(1):13. PMID: 36670464 -
J Chem Inf Model
Discovery of a Novel and Potent LCK Inhibitor for Leukemia Treatment via Deep Learning and Molecular Docking. [Abstract]2024 Jun 24;64(12):4835-4849. PMID: 38847742 -
Int J Mol Sci
2024 Sep 21;25(18):10138. PMID: 39337621 -
Braz J Med Biol Res
FRAX486, a PAK inhibitor, overcomes ABCB1-mediated multidrug resistance in breast cancer cells. [Abstract]2024 Jul 1:57:e13357. PMID: 38958364 -
bioRxiv
Network analysis of α-synuclein pathology progression reveals p21-activated kinases as regulators of vulnerability. [Abstract]2024 Oct 22:2024.10.22.619411. PMID: 39484617 -
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Solvent & Solubility
DMSO : 10 mg/mL (19.48 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Protocol
WPMY-1 cells are plated with a density of 50,000/well on a 16-well chambered coverslip. After 24 h, cells are treated with FRAX486 (1, 5, 10 μM), IPA3 (1, 5, 10 μM), or DMSO. After further 24 h, the medium is changed to a 10 mM 5-ethynyl-2’-deoxyuridine (EdU) solution in FCS-free medium containing inhibitors or solvent. 20 h later, cells were fixed with 3.7% formaldehyde. EdU incorporation is determined using the “EdU-Click 555” cell proliferation assay. In this assay, incorporation of EdU into DNA is assessed by detection with fluorescing 5-carboxytetramethylrhodamine (5-TAMRA). Counterstaining of all nuclei is performed with DAPI. Cells are analyzed by fluorescence microscopy (excitation: 546 nm; emission: 479 nm)[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Mice[2]
The fasted male C57BL/6 mice are used. For FRAX486, i.v. dose is 3 mg/kg using a 1 mg/mL solution in 20% (wt/vol) 2-hydroxypropyl-β-cyclodextrin in water, and per oral administration (o.s.) (PO) dose is 30 mg/kg in a 3 mg/mL solution in water. For the in vivo experiment, FRAX486 is intraperitoneally administered [10 μg/BW (g)] once daily from P35 to P60, which provides brain levels at >175 nM.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
Purity & Documentation
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Data Sheet (278 KB)
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SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Portuguese - PT (393 KB)
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Handling Instructions (2659 KB)
References
[1]. Wang Y, et al. P21-Activated Kinase Inhibitors FRAX486 and IPA3: Inhibition of Prostate Stromal Cell Growth and Effects on Smooth Muscle Contraction in the Human Prostate. PLoS One. 2016 Apr 12;11(4):e0153312. [Content Brief]
[2]. Hayashi-Takagi A, et al. PAKs inhibitors ameliorate schizophrenia-associated dendritic spine deterioration in vitro and in vivo during late adolescence. Proc Natl Acad Sci U S A. 2014 Apr 29;111(17):6461-6. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 2 years; -20°C, 1 year. When stored at -80°C, please use it within 2 years. When stored at -20°C, please use it within 1 year.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 1.9478 mL | 9.7392 mL | 19.4784 mL | 48.6959 mL |
| 5 mM | 0.3896 mL | 1.9478 mL | 3.8957 mL | 9.7392 mL | |
| 10 mM | 0.1948 mL | 0.9739 mL | 1.9478 mL | 4.8696 mL | |
| 15 mM | 0.1299 mL | 0.6493 mL | 1.2986 mL | 3.2464 mL |
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