FRAX486 |
Catalog No.GC16075
One-Click Copy Product Info
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FRAX486은 PAK1, PAK2 및 PAK3에 대해 IC50이 각각 14, 33 및 39nM인 p21 활성화 키나제(PAK) 억제제입니다.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 1232030-35-1
Sample solution is provided at 25 µL, 10mM.
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IC50: 14, 33, 39 and 575 nM for PAK1, PAK2, PAK3 and PAK4 respectively
FRAX486 is a p21-activated kinase (PAK) inhibitor.
PAKs are known as effector proteins for the Rho GTPases Cdc42 and Rac. Both in vitro and in vivo studies have showed PAKs play critical roles for cytoskeletal organization and in various aspects of cell growth and development.
In vitro: Previous study showed in WPMY-1 cells, FRAX486 could dose-dependently induce the degeneration of actin filaments, which was accompanied by proliferation rate attenuation. Moreover, the FRAX486 cytotoxicity in WPMY-1 cells was found to be both time- and concentration-dependent. In addition, the effects of FRAX486 on actin organization, survival, and proliferation were observed at 1-5 μM in WPMY-1 cells, and complete inhibition of PAK1-3 might be expected, whereas PAK4 might be inhibited only partially at these concentrations [1].
In vivo: Animal study found that FRAX486 was able to cross the blood-brain barrier (BBB) and the brain therapeutical FRAX486 concentrations were detected as early as 1 h and remained as long as 24 h, with the maximum concentration (Cmax) at 8 h. Moreover, FRAX486 could reduce hyperactivity and stereotypical movements, both of which were phenotypes characterizing the Fragile X syndrome mouse model [2].
Clinical trial: Up to now, FRAX486 is still in the preclinical development stage.
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.
[2] Dolan BM,Duron SG,Campbell DA,Vollrath B,Shankaranarayana Rao BS,Ko HY,Lin GG,Govindarajan A,Choi SY,Tonegawa S. Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486. Proc Natl Acad Sci U S A. 2013 Apr 2;110(14):5671-6.
Cell experiment: | 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]. |
Animal experiment: | 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. |
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. | |
| Cas No. | 1232030-35-1 | SDF | |
| Chemical Name | 6-(2,4-dichlorophenyl)-8-ethyl-2-((3-fluoro-4-(piperazin-1-yl)phenyl)amino)pyrido[2,3-d]pyrimidin-7(8H)-one | ||
| Canonical SMILES | O=C1C(C2=CC=C(Cl)C=C2Cl)=CC3=CN=C(NC4=CC=C(N5CCNCC5)C(F)=C4)N=C3N1CC | ||
| Formula | C25H23Cl2FN6O | M.Wt | 513.39 |
| Solubility | <2.59 mg/mL in DMSO, <2.62 mg/mL in ETOH, <2.56 mg/mL in Water | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.9478 mL | 9.7392 mL | 19.4784 mL |
| 5 mM | 389.6 μL | 1.9478 mL | 3.8957 mL |
| 10 mM | 194.8 μL | 973.9 μL | 1.9478 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL saline, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 13 reference(s) in Google Scholar.)